반응 #328379

반응 방정식

2-Fluoroethylamine hydrochloride salt

DIPEA

thiophosgene

4-Bromobenzene-1,2-diamine

→

5-bromo-N-(2-fluoroethyl)-1H-benzo[d]imidazol-2-amine

수율 54.0%

용매

DCM

THF

THF

반응 조건

후처리

1. 1
   온도to slowly warm to room temperature over 30 minutes
2. 2
   농축The mixture was concentrated
3. 3
   기타the residue partitioned with ethyl acetate and 10% aqueous citric acid
4. 4
   세척The organic phase was washed twice with additional 10% aqueous citric acid
5. 5
   건조brine, dried over anhydrous sodium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   workup.ADDITIONThe crude mixture of thiourea
9. 9
   기타thus obtained
10. 10
    온도to reflux for 6 h
11. 11
    workup.STIRRINGthen stirred an additional 60 h at room temperature
12. 12
    여과The crude mixture was filtered through a bed of celite with ethyl acetate washing
13. 13
    농축the filtrate concentrated
14. 14
    세척The organic solution was washed once with 1 M aqueous hydrochloric acid
15. 15
    여과The aqueous phase was filtered
16. 16
    기타to remove trace insoluble residue
17. 17
    workup.ADDITIONthe filtrate basified to pH 9-10 by dropwise addition of 50% aqueous sodium hydroxide
18. 18
    추출The aqueous phase was then extracted once with ethyl acetate
19. 19
    세척the organic solution was washed with brine
20. 20
    건조then dried over anhydrous sodium sulfate
21. 21
    여과filtered
22. 22
    농축concentrated

실험 절차

2-Fluoroethylamine hydrochloride salt (282.4 mg, 2.83 mmol) was suspended in 1:1 THF:DCM (6 mL) followed by addition of DIPEA (2.5 mL, 14.35 mmol). The mixture was cooled to 0° C. followed by slow addition of thiophosgene (217 uL, 2.8 mmol) by syringe over five minutes then allowed to slowly warm to room temperature over 30 minutes. 4-Bromobenzene-1,2-diamine (530 mg, 2.8 mmol) was then added and the reaction mixture was allowed to stir at room temperature over an additional 12 h. The mixture was concentrated and the residue partitioned with ethyl acetate and 10% aqueous citric acid. The organic phase was washed twice with additional 10% aqueous citric acid then brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude mixture of thiourea thus obtained was taken into THF (15 mL) followed by addition of mercury (II) oxide (640 mg, 2.95 mmol). The mixture was brought to reflux for 6 h then stirred an additional 60 h at room temperature. The crude mixture was filtered through a bed of celite with ethyl acetate washing and the filtrate concentrated then taken back into ethyl acetate. The organic solution was washed once with 1 M aqueous hydrochloric acid and the organic phase discarded. The aqueous phase was filtered to remove trace insoluble residue and the filtrate basified to pH 9-10 by dropwise addition of 50% aqueous sodium hydroxide. The aqueous phase was then extracted once with ethyl acetate and the organic solution was washed with brine then dried over anhydrous sodium sulfate, filtered and concentrated to afford crude 5-bromo-N-(2-fluoroethyl)-1H-benzo[d]imidazol-2-amine (390 mg, 53% yield) which was carried forward without further purification. MS (EI) for C9H9BrFN3: 258, 260 (MH+).

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