반응 #487578

ord-fdc6908d19524ed9b2665ac855ac0b3c

반응 방정식

O=C(n1ccnc1)n1ccnc1
carbonyldiimidazole
NCCN1CCOCC1
4-(2-aminoethyl)morpholine
N#Cc1ccc(Oc2cc(Cl)cc(Cl)c2)c(S(=O)(=O)N2CCC(N)CC2)c1
3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)-benzonitrile
CC(C)OC(C)C
isopropyl ether
N#Cc1ccc(Oc2cc(Cl)cc(Cl)c2)c(S(=O)(=O)N2CCC(NC(=O)NCCN3CCOCC3)CC2)c1
1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)-piperidin-4-yl)-3-(2-morpholinoethyl)urea
N#Cc1ccc(Oc2cc(Cl)cc(Cl)c2)c(S(=O)(=O)N2CCC(NC(=O)NCCN3CCOCC3)CC2)c1
1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)piperidin-4-yl)-3-(2-morpholinoethyl)urea

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타was consumed (confirmed by HPLC)
  2. 2
    workup.STIRRINGthe mixture was stirred 19 hours
  3. 3
    농축Concentration in vacuo
  4. 4
    기타provided a white solid, which
  5. 5
    기타partitioned with water
  6. 6
    추출the aqueous layer extracted three times with dichloromethane
  7. 7
    세척The combined organic layers were washed with brine
  8. 8
    건조dried over anhydrous magnesium sulfate
  9. 9
    여과filtered
  10. 10
    농축concentrated in vacuo
  11. 11
    기타to yield a white solid

실험 절차

1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)-piperidin-4-yl)-3-(2-morpholinoethyl)urea (22) is prepared according to the following method as an alternative to the method of Example 32. 3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)-benzonitrile (1.002 g), prepared according to Example 1, and carbonyldiimidazole (420 mg, 1.1 eq.) were combined in THF (15 mL) and stirred at room temperature. After 5 hours, starting material was consumed (confirmed by HPLC). 4-(2-aminoethyl)morpholine (512 mg, 2.0 eq.) was added and the mixture was stirred 19 hours. Concentration in vacuo provided a white solid, which was resuspended in dichlormethane, partitioned with water, and the aqueous layer extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield a white solid. Trituration with isopropyl ether yielded a 96% pure product according to HPLC. The powder was suspended in minimal amounts of hot methanol, stirred at 60° C. for 30 minutes, cooled in an ice bath and vacuum filtered to obtain the product as a white powder (831 mg, 60.7% yield, 98% purity).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08741894B2uspto-grants-2014_06