4-Methylmorpholine → (1S,3aR,6aS)-2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide

HRID 424972ノート

反応式

HRID 424972 の反応式
[CH:1]1([CH:7]([NH:34][C:35](C2C=NC=CN=2)=[O:36])[CH:8]([NH:13][CH:14]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:15]([N:17]2[CH2:21][C@@H:20]3[CH2:22][CH2:23][CH2:24][C@@H:19]3[C@H:18]2C(OCC)=O)=[O:16])[C:9]([F:12])([F:11])[F:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].C1(C(NC([C:79]2[CH:84]=[N:83][CH:82]=[CH:81][N:80]=2)=O)C(NC(C(C)(C)C)C(N2C[C@@H]3CCC[C@@H]3[C@H]2C(O)=O)=O)C(F)(F)F)CCCCC1.CN1CC[O:89][CH2:88]C1.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.Cl.[NH2:114][C@@H:115]([CH2:124][CH2:125][CH3:126])[CH:116]([OH:123])[C:117]([NH:119][CH:120]1[CH2:122][CH2:121]1)=[O:118]>C(O)C.C(OCC)(=O)C.O1CCCC1.ClCCl>[CH:1]1([CH:7]([NH:34][C:35]([C:84]2[CH:79]=[N:80][CH:81]=[CH:82][N:83]=2)=[O:36])[CH:8]([NH:13][CH:14]([C:30]([CH3:32])([CH3:33])[CH3:31])[C:15]([N:17]2[CH2:21][C@@H:20]3[CH2:22][CH2:23][CH2:24][C@@H:19]3[C@H:18]2[C:88]([NH:114][C@@H:115]([CH2:124][CH2:125][CH3:126])[CH:116]([OH:123])[C:117]([NH:119][CH:120]2[CH2:121][CH2:122]2)=[O:118])=[O:89])=[O:16])[C:9]([F:11])([F:10])[F:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

12

反応物 7

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 66656935Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (3S)-HCID 66704743(1S,3aR,6aS)-2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acidHCID 86635382(1S,3aR,6aS)-ethyl 2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate

生成物 1

HCID 66704750(1S,3aR,6aS)-2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

The stereoisomer of (1S,3aR,6aS)-ethyl 2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate, designated as 10A1-isomer-A (85 mg) was dissolved in ethanol (3 mL) and treated with 2N aqueous sodium hydroxide solution (0.665 mL) at 65° C. for 2 hours. The reaction mixture was then diluted with ethyl acetate and washed successively with 1N hydrochloric acid, water, brine and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave the crude acid, designated as 11A1-isomer A, an isomer of (1S,3aR,6aS)-2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid. The crude compound of formula 11A1-isomer A was mixed with N-methylmorpholine (0.078 mL, 5 eq), 1-hydroxybenzotriazole (38.6 mgm, 2 eq), 1-ethyl-3-(3′-dimethylaminopropyl)carbodimide (55 mgm, 2 eq), and (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride (12) (123 mgm, 4 eq) and dissolved in a mixture of tetrahydrofuran and dichloromethane, and stirred at room temperature for 18 hours. The reaction mixture was then diluted with ethyl acetate, washed successively with 1N hydrochloric acid, water, brine and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave crude product (13A1-isomer A), an isomer of (1S,3aR,6aS)-2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide.

後処理

  1. washwashed successively with 1N hydrochloric acid, water, brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. customEvaporation to dryness under reduced pressure
  4. customgave the crude acid
  5. washwashed successively with 1N hydrochloric acid, water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customEvaporation to dryness under reduced pressure

出典と根拠

ORDレコード
ord-edcb747f589149808530c68a1bfe2484
出典データセット
uspto-grants-2012_01
特許番号
US08106059B2

反応ノート

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