Acetic Anhydride → HCID 67024770, compound

HRID 488428Notes

Reaction equation

HRID 488428 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:44][CH2:45][CH:46]4[CH2:48][CH2:47]4)=[C:24]([NH:27][C:28](=[O:43])[CH:29]=[CH:30][CH2:31][N:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH:33]4[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15].C(N(CC)CC)C>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:44][CH2:45][CH:46]4[CH2:47][CH2:48]4)=[C:24]([NH:27][C:28](=[O:43])[CH:29]=[CH:30][CH2:31][N:32]4[CH2:37][CH2:36][N:35]([C:1]([CH3:2])=[O:3])[CH2:34][CH:33]4[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[F:15]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 54189909HCID 54189909, compound

Product 1

HCID 67024770HCID 67024770, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

0.12 ml of acetic acid anhydride are added dropwise to a mixture of 500 mg of 4-[(3-chloro-4-fluoro-phenyl)amino]-6-({4-[2-(ethoxycarbonyl)-piperazin-1-yl]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline and 0.18 ml of triethylamine in 5 ml of methylene chloride at 0° C. The reaction mixture is stirred for one hour at 0° C. followed by one hour at room temperature, washed with water, concentrated sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The crude product is purified by column chromatography on silica gel with ethyl acetate/methanol (98:2 to 95:5). Yield: 291 mg (54% of theory), Melting point: 152-156° C. Mass spectrum (ESI+): m/z=625, 627 [M+H]+

Workup

  1. waitfollowed by one hour at room temperature
  2. washwashed with water, concentrated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product is purified by column chromatography on silica gel with ethyl acetate/methanol (98:2 to 95:5)

Sources & evidence

ORD record
ord-c5da6778688a46278a35410f14e485ae
Source dataset
uspto-grants-2005_12
Patent number
US06972288B1

Reaction notes

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