反应 #42972

反应方程式

ammonia

Thiophosgene

solution

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

DIEA

Bromopyruvic acid

→

title compound

收率 75.0%

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

收率 75.0%

溶剂

THF

反应条件

后处理

1. 1
   萃取extracted with EtOAc
2. 2
   干燥Organics were dried (MgSO4)
3. 3
   浓缩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
   其他Purification by silica gel chromatography (10% MeOH/CHCl3)

实验过程

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.

来源