Triethylamine → tert-Butyl [(1R,3S)-3-(2-methoxyethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate

HRID 1044623ノート

反応式

HRID 1044623 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([CH2:17][CH2:18][O:19][CH3:20])([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([CH2:17][CH2:18][O:19][CH3:20])([C:14]([N:34]2[CH2:35][CH2:36][N:31]([C:27]3[CH:26]=[C:25]([C:24]([F:38])([F:23])[F:37])[CH:30]=[CH:29][N:28]=3)[CH2:32][CH2:33]2)=[O:16])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59833582(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-(2-methoxyethyl)cyclopentanecarboxylic acidHCID 685975881-[4-(Trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride

生成物 1

HCID 59833567tert-Butyl [(1R,3S)-3-(2-methoxyethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate収率 52.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-(2-methoxyethyl)cyclopentanecarboxylic acid (276.6 mg, 0.96 mmol), 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride (322.0 rug, 1.06 mmol), triethylamine (0.54 mL, 3.85 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (547.6 mg, 1.44 mmol) (HBTU) were mixed in dry DMF (6.6 mL) and the resultanting brown solution was stirred at room temperature under N2 for three days. The reaction mixture was diluted with CH2Cl2, and washed with saturated Na2CO3. The aqueous layer was extracted with CH2Cl2 four times. The combined organic layers were dried (MgSO4), filtered, concentrated and purified by flash chromatography (EtOAc/Hexane) to provide the desired product (252 mg, 52%). MS calculated for C24H36F3N4O4 (M+H) 501.3; found 401.3 (M+H-Boc).

後処理

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with CH2Cl2 four times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (EtOAc/Hexane)

出典と根拠

ORDレコード
ord-97d49e9221924319b9ea08827be03ad3
出典データセット
uspto-grants-2013_10
特許番号
US08563582B2

反応ノート

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