Acetic Acid → HCID 71293621, compound

HRID 1402533Notes

Reaction equation

HRID 1402533 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:37]=[CH:36][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][CH:34]=O)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11].[NH:38]1[CH2:43][CH2:42][CH2:41][CH:40]([CH2:44][OH:45])[CH2:39]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][CH2:34][N:38]4[CH2:43][CH2:42][CH2:41][CH:40]([CH2:44][OH:45])[CH2:39]4)=[O:30])[CH:25]=3)[CH:19]=2)=[CH:36][CH:37]=1)=[O:11]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 107308Piperidin-3-ylmethanolHCID 5003444Sodium cyanoborohydrideHCID 71542909HCID 71542909, compound

Product 1

HCID 71293621HCID 71293621, 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-(3-oxopropyl)-1H-pyrrole-3-carboxamide (120 mg, 0.24 mmol) and 3-piperidinemethanol (56 mg, 0.49 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 (0.5 ml, 0.5 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 10˜20% methanol/chloroform solution to give 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-N-{3-[3-(hydroxymethyl)piperidin-1-yl]propyl}-1H-pyrrole-3-carboxamide as white solid. Yield: 58 mg, 40%.

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 10˜20% methanol/chloroform solution

Sources & evidence

ORD record
ord-56ae553e4d6a4b77a5f11c22c7b7e713
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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