Acetic Acid → HCID 71293504, compound

HRID 1402580Notes

Reaction equation

HRID 1402580 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([NH:11][C:12]2[CH:36]=[CH:35][C:15]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[NH:27][CH:26]=[C:25]([C:28]([NH:30][CH2:31][CH2:32][CH:33]=O)=[O:29])[CH:24]=4)[CH:18]=3)=[CH:14][CH:13]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.[OH:37][CH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1>CN(C=O)C.O>[OH:37][CH:38]1[CH2:43][CH2:42][N:41]([CH2:33][CH2:32][CH2:31][NH:30][C:28]([C:25]2[CH:24]=[C:23]([C:19]3[CH:18]=[C:17]([O:16][C:15]4[CH:14]=[CH:13][C:12]([NH:11][C:9]([NH:8][C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=5)=[O:10])=[CH:36][CH:35]=4)[CH:22]=[CH:21][N:20]=3)[NH:27][CH:26]=2)=[O:29])[CH2:40][CH2:39]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 79341Piperidin-4-olHCID 5003444Sodium cyanoborohydrideHCID 86678333HCID 86678333, compound

Product 1

HCID 71293504HCID 71293504, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-{4-[4-({[(3-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-N-(3-oxopropyl)-1H-pyrrole-3-carboxamide (150 mg, 0.31 mmol) in 10 ml of anhydrous DMF were added 4-hydroxypiperidine (59 mg, 0.58 mmol) and acetic acid (10 mg, 0.17 mmol). The mixture was stirred at room temperature for 60 minutes, followed by addition of 1M sodium cyanoborohydride solution in THF (0.60 ml, 0.60 mmol). Stirring was continued for another 60 minutes and the mixture was poured into 50 ml of water. The precipitates were filtered, washed with water and dried to give the crude, which was purified by silica gel flash chromatography eluting with 20% of MeOH in CHCl3 to give N-[3-(4-hydroxypiperidin-1-yl)propyl]-5-{4-[4-({[(3-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxamide as off-white solid. Yield: 102 mg, 58%.

Workup

  1. stirringStirring
  2. waitwas continued for another 60 minutes
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried
  6. customto give the crude, which
  7. customwas purified by silica gel flash chromatography
  8. washeluting with 20% of MeOH in CHCl3

Sources & evidence

ORD record
ord-42b95080ec2c4869a3ffa6e2e9b36fea
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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