Sodium Bicarbonate → HCID 57813967, compound

HRID 564394Notes

Reaction equation

HRID 564394 reaction equation
[OH:1][C@@H:2]1[CH2:6][NH:5][CH2:4][C@H:3]1[NH:7][C:8](=[O:23])[CH2:9][NH:10][C:11](=[O:22])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1.[CH3:24][O:25][C:26]1[N:31]=[CH:30][C:29]([N:32]2[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]2)=[CH:28][CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.ClCCl>[OH:1][C@H:2]1[CH2:6][N:5]([CH:35]2[CH2:36][CH2:37][N:32]([C:29]3[CH:30]=[N:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[CH2:33][CH2:34]2)[CH2:4][C@@H:3]1[NH:7][C:8](=[O:23])[CH2:9][NH:10][C:11](=[O:22])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 220002791-(6-Methoxypyridin-3-yl)piperidin-4-oneHCID 67005109HCID 67005109, compound

Product 1

HCID 57813967HCID 57813967, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of rac-N-(2-{[(3R,4R)-4-hydroxypyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide (50 mg, 0.152 mmol; prepared according to WO2004/050024A2), 1-(6-methoxypyridin-3-yl)piperidin-4-one (31 mg, 0.151 mmol) in methanol (4 mL) was added sodium triacetoxyborohydride (37 mg, 1.74 mmol) and stirred overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3S,4S)-4-hydroxy-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (73 mg, 93%) as a white solid. 1H-NMR (CD3OD) δ: 1.56-1.70 (m, 1H), 1.95-2.06 (m, 1H), 2.20-2.30 (m, 1H), 2.54-2.75 (m, 5H), 3.05-3.14 (m, 3H), 3.30-3.37 (m, 3H), 3.45-3.54 (m, 2H), 3.80-3.86 (s, 3H), 4.03-4.09 (m, 2H), 4.10-4.20 (m, 2H), 6.70-6.76 (in 1H), 7.40-7.50 (m, 1H), 7.69 (t, J=7.8 Hz, 1H), 7.70-7.78 (m, 1H), 7.86 (d, J=7.8 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H), 8.21 (s, 1H). MS m/z: 522 (M+1).

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-18bf288b093b49b6b6b8c0ebb0acb3e4
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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