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 1173210ノート

反応式

HRID 1173210 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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), extrated 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).

後処理

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

出典と根拠

ORDレコード
ord-0fd57764538b47769483d633f4548580
出典データセット
uspto-grants-2010_11
特許番号
US07834021B2

反応ノート

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