Acetyl chloride → HCID 135939119, compound

HRID 591649Notes

Reaction equation

HRID 591649 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[NH:22][C:21](=[O:23])[C:20]4[C:15](=[CH:16][C:17]([O:26][CH3:27])=[CH:18][C:19]=4[O:24][CH3:25])[N:14]=3)=[CH:9][CH:8]=2)[CH2:3]1.CCN(CC)CC.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl>[CH3:25][O:24][C:19]1[CH:18]=[C:17]([O:26][CH3:27])[CH:16]=[C:15]2[C:20]=1[C:21](=[O:23])[NH:22][C:13]([C:10]1[CH:11]=[CH:12][C:7]([N:4]3[CH2:5][CH2:6][CH:2]([NH:1][C:35](=[O:37])[CH3:36])[CH2:3]3)=[CH:8][CH:9]=1)=[N:14]2

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 136348024HCID 136348024, compound

Product 1

HCID 135939119HCID 135939119, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(4-(3-aminopyrrolidin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.150 g, 0.41 mmol) in CH2Cl2 (10 mL) was treated with Et3N (0.114 mL, 0.82 mmol), cooled to 0° C., and acetyl chloride (0.029 mL, 0.41 mmol) was added. The mixture was stirred for 2 hours at room temperature, concentrated, and purified by flash chromatography on silica gel, eluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH. The mixture was further purified by flash chromatography on silica gel, eluting with 9:1 methylene chloride/methanol, to afford the title compound (0.130 g, 78%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ 11.67 (s, 1H), 8.18 (d, J=6.8 Hz, 1H), 8.14 (d, J=6.8 Hz, 2H), 6.66 (d, J=2.3 Hz, 1H), 6.60 (d, J=9.0 Hz, 2H), 6.44 (d, J=2.3 Hz, 1H), 4.36-4.39 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.13-3.59 (m, 5H), 2.15-2.22 (m, 1H), 1.90-1.94 (m, 1H), 1.82 (s, 3H). ESI MS m/z 409 [M+H]+.

Workup

  1. concentrationconcentrated
  2. custompurified by flash chromatography on silica gel
  3. washeluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH
  4. customThe mixture was further purified by flash chromatography on silica gel
  5. washeluting with 9:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-3cdc0ab470b644e59e5d82db9154f4cc
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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