Propylphosphonic anhydride → tert-butyl 1-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

HRID 1036671노트

반응식

HRID 1036671 반응식
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:18])[CH3:17])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]2[C:39]3([CH2:44][CH2:43][CH2:42][NH:41][CH2:40]3)[C:38](=[O:45])[N:37]([CH3:46])[CH2:36]2)=[CH:31][CH:30]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC#N.C(=O)(O)[O-].[Na+].C(Cl)Cl>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:18])[CH3:17])[C:11]([N:41]1[CH2:42][CH2:43][CH2:44][C:39]2([C:38](=[O:45])[N:37]([CH3:46])[CH2:36][CH:35]2[C:32]2[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=2)[CH2:40]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 3

HCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2회HCID 710604314-(4-Fluorophenyl)-2-methyl-2,7-diazaspiro[4.5]decan-1-one

생성물 1

HCID 71060154tert-butyl 1-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate수율 97%

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 516892Sodium Bicarbonate용매

실험 절차

To a stirred solution of (R)-3-benzyloxy-2-(2-tert-butoxycarbonylamino-2-methylpropionylamino)-propionic acid (Intermediate 3A) (344 mg, 0.904 mmol) and 4-(4-fluorophenyl)-2-methyl-2,7-diazaspiro[4.5]decan-1-one (270 mg, 0.904 mmol) in MeCN (4 mL) was added dropwise a solution of ®T3P (50% in EtOAc) (1.055 ml, 1.807 mmol) at room temperature. The resulting colourless solution was stirred for 20 hours. The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL). The aqueous phase was separated and extracted using DCM (3×10 mL), the combined organic fractions were washed with 10% citric acid (10 mL), dried (MgSO4) and then concentrated under reduced pressure to afford tert-butyl 1-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate (546 mg, 97%) as a white amorphous solid.

후처리

  1. customThe aqueous phase was separated
  2. extractionextracted
  3. washthe combined organic fractions were washed with 10% citric acid (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-3b92b0b621154d11ab8394b9e1c435b1
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546416B2

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