Sodium Carbonate → N-[2-({(3R)-1-[4-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 1015999Notes

Reaction equation

HRID 1015999 reaction equation
[N:1]1([C:5]2[N:10]=[CH:9][C:8]([C:11]3([OH:18])[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[NH:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([CH2:27][NH:28][C:29](=[O:40])[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)=[O:26])[CH2:20]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[N:1]1([C:5]2[N:10]=[CH:9][C:8]([C:11]3([OH:18])[CH2:16][CH2:15][CH:14]([N:19]4[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:26])[CH2:27][NH:28][C:29](=[O:40])[C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:39])[F:38])[CH:31]=5)[CH2:20]4)[CH2:13][CH2:12]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 595560894-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexanone

Product 1

HCID 59556061N-[2-({(3R)-1-[4-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(6-azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexanone (115 mg, 0.467 mmol) and N—((R)-pyrrolidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide (140.4 mg, 0.445 mmol) in dry CH2Cl2 (19 mL) was added Na(OAc)3BH (198 mg, 0.934 mmol) in one portion under N2 at rt. The reaction mixture was stirred under N2 overnight (16 h) and treated with Na2CO3 (aq), extracted with CH2Cl2×3, dried, filtered and concentrated to give a crude, which was purified by column chromatography (20:80:0.5 MeOH/EtOAc/NH4OH) to provide 60 mg (25%) of desired isomer product (top spot on TLC) as a white solid. MS (M+H+)=546.1. 1H NMR (CD3OD) δ 8.24 (m, 2H), 8.17 (m, 2H), 7.88 (m, 2H), 7.74 (m, 2H), 6.56 (d, 1H), 4.36 (m, 2H), 4.27 (m, 3H), 4.06 (m, 3H), 3.86 (m, 1H), 3.48 (m, 2H), 3.20 (m, 1H), 2.69 (m, 1H), 2.60 (m, 2H), 2.35-2.30 (m, 4H), 2.20-1.97 (m, 4H), 1.73 (m, 2H).

Workup

  1. extractionextracted with CH2Cl2×3
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a crude, which
  6. customwas purified by column chromatography (20:80:0.5 MeOH/EtOAc/NH4OH)
  7. customto provide 60 mg (25%) of desired isomer product (top spot on TLC) as a white solid

Sources & evidence

ORD record
ord-949b8de4bfd74d6a81af25ec71bcbae6
Source dataset
uspto-grants-2011_07
Patent number
US07985730B2

Reaction notes

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