Sodium triacetoxyborohydride → Rel-n-{2-[((3r,4r)-4-(allyloxy)-1-{1-[4-(morpholin-4-ylcarbonyl)phenyl]piperidin-4-yl}pyrrolidin-3-yl)amino]-2-oxoethyl}-3-(trifluoromethyl)benzamide

HRID 564400Notes

Reaction equation

HRID 564400 reaction equation
[CH2:1]([O:4][C@@H:5]1[CH2:9][NH:8][CH2:7][C@H:6]1[NH:10][C:11](=[O:26])[CH2:12][NH:13][C:14](=[O:25])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)[CH:2]=[CH2:3].[N:27]1([C:33]([C:35]2[CH:40]=[CH:39][C:38]([N:41]3[CH2:46][CH2:45][C:44](=O)[CH2:43][CH2:42]3)=[CH:37][CH:36]=2)=[O:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH2:1]([O:4][C@@H:5]1[CH2:9][N:8]([CH:44]2[CH2:43][CH2:42][N:41]([C:38]3[CH:37]=[CH:36][C:35]([C:33]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[O:34])=[CH:40][CH:39]=3)[CH2:46][CH2:45]2)[CH2:7][C@H:6]1[NH:10][C:11](=[O:26])[CH2:12][NH:13][C:14](=[O:25])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 670046941-[4-(Morpholin-4-ylcarbonyl)phenyl]piperidin-4-oneHCID 67005293Rel-n-(2-{[(3r,4r)-4-(allyloxy)pyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 67004679Rel-n-{2-[((3r,4r)-4-(allyloxy)-1-{1-[4-(morpholin-4-ylcarbonyl)phenyl]piperidin-4-yl}pyrrolidin-3-yl)amino]-2-oxoethyl}-3-(trifluoromethyl)benzamideYield 55.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the solution of rel-N-(2-{[(3R,4R)-4-(allyloxy)pyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide (60 mg, 0.16 mmol) in methanol (5 mL) was added 1-[4-(morpholin-4-ylcarbonyl)phenyl]piperidin-4-one (70 mg, 0.24 mmol) and sodium triacetoxyborohydride (68.5 mg, 0.32 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched by adding water (5 mL), and mixture then was extracted with EtOAc (15 mL×3). The organic phases were combined, dried over MgSO4, filtered, concentrated under reduced pressure and subjected to column chromatography (ethyl acetate, methanol and ammonium hydroxide (85:15:1) to afford the title compound (57 mg, 55%) as a white solid. 1H-NMR (CDCl3) δ: 1.44-1.62 (m, 2H), 1.79-1.88 (m, 2H), 2.00-2.18 (m, 2H), 2.24-2.37 (m, 2H), 2.61-2.68 (m, 4H), 3.25-3.33 (r, 1H), 3.59-3.68 (m, 8H), 3.78-3.79 (m, 1H), 3.92-3.99 (m, 1H), 4.05 (d, J=4.8 Hz, 2H), 4.08-4.16 (m, 1H), 4.27 (b, 1H), 5.09-5.25 (m, 2H), 5.76-5.89 (m, 1H), 6.81 (d, J=8.4 Hz, 2H), 7.27 (d, J=8.1 Hz, 2H), 7.47-7.52 (m, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 8.03 (s, 1H). MS m/z: 644 (M+1).

Workup

  1. customThe reaction was quenched
  2. additionby adding water (5 mL), and mixture
  3. extractionthen was extracted with EtOAc (15 mL×3)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-20c0ae3f4329405a81132a30ed36df82
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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