Acetic Acid → HCID 71542815, compound

HRID 1402532Notes

Reaction equation

HRID 1402532 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:36]=[CH:35][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([NH:31][CH2:32][CH:33]=O)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11].[N:37]1([CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:14]=[CH:15][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([NH:31][CH2:32][CH2:33][N:40]4[CH2:41][CH2:42][N:37]([CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:38][CH2:39]4)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:35][CH:36]=1)=[O:11]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 207112Ethyl piperazine-1-acetateHCID 5003444Sodium cyanoborohydrideHCID 71542907HCID 71542907, compound

Product 1

HCID 71542815HCID 71542815, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-N-(2-oxoethyl)-1H-pyrrole-3-carboxamide (200 mg, 0.41 mmol) and ethyl piperazinoacetate (141 mg, 0.82 mmol) in anhydrous DMF (10 ml) was added acetic acid (10 mg, 0.17 mmol). The mixture was stirred under nitrogen for 30 minutes, followed by addition of 1M sodium cyanoborohydride solution in THF (0.8 ml, 0.8 mmol). The reaction mixture was stirred for another hour, and poured into 100 ml of water with vigorous stirring. The precipitates were filtered, washed with water, and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with a gradient of 8˜12% methanol/chloroform solution to give ethyl [4-(2-{[(5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}ethyl)piperazin-1-yl]acetate as white solid. Yield: 90 mg, 34%.

Workup

  1. stirringThe reaction mixture was stirred for another hour
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried in vacuo
  5. customto give the crude, which
  6. customwas purified by silica gel chromatography
  7. washeluting with a gradient of 8˜12% methanol/chloroform solution

Sources & evidence

ORD record
ord-f66e1331496a485a82903321486baebc
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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