反応 #42972

反応方程式

ammonia

Thiophosgene

solution

2-(4-Amino-6,8-dimethoxy-isoquinolin-1-ylmethyl)-isoindole-1,3-dione

DIEA

Bromopyruvic acid

→

title compound

収率 75.0%

2-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6,8-dimethoxy-isoquinolin-4-ylamino]-thiazole-4-carboxylic acid

収率 75.0%

溶媒

THF

反応条件

後処理

1. 1
   抽出extracted with EtOAc
2. 2
   乾燥Organics were dried (MgSO4)
3. 3
   濃縮concentrated
4. 4
   workup.DISSOLUTIONThe resulting crude thiourea was dissolved in THF (5 mL)
5. 5
   workup.STIRRINGthe reaction stirred for 2 h
6. 6
   その他Purification by silica gel chromatography (10% MeOH/CHCl3)

実験手順

Thiophosgene (146 μL, 1.92 mmol) was added to a solution of Example 45C (580 mg, 1.6 mmol) and DIEA (670 μL) in THF (10 mL). After stirring for 1 h, the reaction was poured over aqueous ammonia and extracted with EtOAc. Organics were dried (MgSO4) and concentrated. The resulting crude thiourea was dissolved in THF (5 mL). Bromopyruvic acid (320 mg, 1.92 mmol) was added, and the reaction stirred for 2 h. Purification by silica gel chromatography (10% MeOH/CHCl3) gave 590 mg (75%) of the title compound as a tan solid. H1-NMR (MeOD-d4): δ 9.95 (br s, 1H), 8.81 (br s, 1H), 7.87-7.96 (m, 4H), 7.60 (br s, 1H), 7.14 (s, 1H), 6.86 (s, 1H), 5.41 (s, 2H), 4.09 (s, 3H), 3.94 (s, 3H). MS (ES) (M+H) calc'd for C24H18N4O6S, 491; found 491.

出典