Acetic Acid → 7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-[3-(4-hydroxypiperidin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide

HRID 525810Notes

Reaction equation

HRID 525810 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[NH:25][C:26]([NH:28][C:29]1[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=1[F:36])=[O:27])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[CH:12]=[C:13]([C:15]([NH:17]CCC=O)=[O:16])[S:14][C:7]=12.[OH:37][CH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.C(O)(=O)C.C([BH3-])#N.[Na+].[CH2:52]1[CH2:56]OC[CH2:53]1>CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[NH:25][C:26]([NH:28][C:29]1[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=1[F:36])=[O:27])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[CH:12]=[C:13]([C:15]([NH:17][CH2:53][CH2:52][CH2:56][N:41]3[CH2:42][CH2:43][CH:38]([OH:37])[CH2:39][CH2:40]3)=[O:16])[S:14][C:7]=12

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 79341Piperidin-4-olHCID 5003444Sodium cyanoborohydrideHCID 1176900397-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-(3-oxopropyl)thieno[3,2-b]pyridine-2-carboxamide

Product 1

HCID 862907967-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-[3-(4-hydroxypiperidin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-(3-oxopropyl)thieno[3,2-b]pyridine-2-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 40 minutes, followed by addition of 1M sodium cyanoborohydride solution in THF (0.60 ml, 0.60 mmol) and stirring was continued for another 30 minutes. The mixture was poured into 100 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 10-20% of MeOH in CHCl3 to give 7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-[3-(4-hydroxypiperidin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide as white solid. Yield: 70 mg, 40%.

Workup

  1. stirringstirring
  2. waitwas continued for another 30 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 10-20% of MeOH in CHCl3

Sources & evidence

ORD record
ord-2385cf2c79b44a8781418a7e7a7a9ac6
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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