Tetrahydrofuran → HCID 71293676, compound

HRID 1402554Notes

Reaction equation

HRID 1402554 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]3[NH:17][CH:16]=[C:15]([C:18]([NH:20][CH2:21][CH2:22][CH:23]=O)=[O:19])[CH:14]=3)[CH:8]=2)=[CH:4][C:3]=1[NH:27][C:28]([C:30]1[O:31][CH:32]=[CH:33][C:34]=1[CH3:35])=[O:29].Cl.[CH3:37][O:38][C:39](=[O:45])[C@@H:40]1[CH2:44][CH2:43][CH2:42][NH:41]1.C(N(CC)CC)C.C([BH3-])#N.[Na+].C1COCC1>CN(C=O)C.O>[F:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]3[NH:17][CH:16]=[C:15]([C:18]([NH:20][CH2:21][CH2:22][CH2:23][N:41]4[CH2:42][CH2:43][CH2:44][CH:40]4[C:39]([O:38][CH3:37])=[O:45])=[O:19])[CH:14]=3)[CH:8]=2)=[CH:4][C:3]=1[NH:27][C:28]([C:30]1[O:31][CH:32]=[CH:33][C:34]=1[CH3:35])=[O:29]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 2733200methyl L-prolinate hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 71541978HCID 71541978, compound

Product 1

HCID 71293676HCID 71293676, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(4-{4-fluoro-3-[(3-methyl-2-furoyl)amino]phenoxy}pyridin-2-yl)-N-(3-oxopropyl)-1H-pyrrole-3-carboxamide (140 mg, 0.29 mmol) in 10 ml of anhydrous DMF were added L-proline methyl ester hydrochloride (96 mg, 0.58 mmol) and triethylamine (58 mg, 0.58 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 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 5% of MeOH in CHCl3 to give methyl 1-[3-({[5-(4-{4-fluoro-3-[(3-methyl-2-furoyl)amino]phenoxy}pyridin-2-yl)-1H-pyrrol-3-yl]carbonyl}amino)propyl]pyrrolidine-2-carboxylate as light beige 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 5% of MeOH in CHCl3

Sources & evidence

ORD record
ord-5b09c82262504ab6a8e3d96b8555a759
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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