Acetic Acid → HCID 71293615, compound

HRID 1402559Notes

Reaction equation

HRID 1402559 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[NH:27][C:28]([NH:30][C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=1[F:38])=[O:29])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([NH:19][CH2:20][CH2:21][CH:22]=O)=[O:18])[CH:13]=2)[CH:7]=1.[OH:39][CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1>CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[NH:27][C:28]([NH:30][C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=1[F:38])=[O:29])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([NH:19][CH2:20][CH2:21][CH2:22][N:43]3[CH2:44][CH2:45][CH:40]([OH:39])[CH2:41][CH2:42]3)=[O:18])[CH:13]=2)[CH:7]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 79341Piperidin-4-olHCID 5003444Sodium cyanoborohydrideHCID 86678331HCID 86678331, compound

Product 1

HCID 71293615HCID 71293615, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-N-(3-oxopropyl)-1H-pyrrole-3-carboxamide (150 mg, 0.29 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 30 minutes, followed by addition of 1M sodium cyanoborohydride solution in THF (0.60 ml, 0.60 mmol) and stirring was continued for another 60 minutes. 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 5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-N-[3-(4-hydroxypiperidin-1-yl)propyl]-1H-pyrrole-3-carboxamide as white solid. Yield: 110 mg, 63%.

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-7358ec3559a14f3989bdb9b8f9fa72b6
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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