Diisopropylethylamine → tert-butyl (4R)-7,10,10,11,11-pentamethyl-4-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decane-7-carbonyl)-6-oxo-1-phenyl-2,9-dioxa-5-aza-10-siladodecan-7-ylcarbamate

HRID 1036685노트

반응식

HRID 1036685 반응식
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:22])([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[NH2:50][C@H:51]([CH2:72][O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)[C:52]([N:54]1[CH2:71][CH2:70][CH2:69][C:56]2([C:60](=[O:61])[N:59]([CH3:62])[CH2:58][CH:57]2[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:55]1)=[O:53]>CN(C=O)C.Cl>[CH3:22][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])([CH2:13][O:14][Si:15]([CH3:17])([CH3:16])[C:18]([CH3:20])([CH3:21])[CH3:19])[C:10](=[O:12])[NH:50][C@@H:51]([C:52]([N:54]1[CH2:71][CH2:70][CH2:69][C:56]2([C:60](=[O:61])[N:59]([CH3:62])[CH2:58][CH:57]2[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:55]1)=[O:53])[CH2:72][O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 710604067-((R)-2-amino-3-(benzyloxy)propanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one2회HCID 866740972-(Tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-methylpropanoic acid2회

생성물 1

HCID 86674096tert-butyl (4R)-7,10,10,11,11-pentamethyl-4-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decane-7-carbonyl)-6-oxo-1-phenyl-2,9-dioxa-5-aza-10-siladodecan-7-ylcarbamate

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6228Dimethylformamide용매2회

실험 절차

A mixture comprising 2-(tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-methylpropanoic acid (intermediate from step 1) (311 mg, 0.934 mmol) and DIPEA (0.652 ml, 3.73 mmol) in DMF (5 mL) was treated with a solution of ®T3P (50% in EtOAc) (1.090 ml, 1.867 mmol) dropwise at room temperature. The resulting solution was stirred for 15 minutes, then 7-((R)-2-amino-3-(benzyloxy)propanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (intermediate from step 3) (500 mg, 0.934 mmol) in DMF (1 mL) was added dropwise at room temperature. The reaction mixture was stirred for 20 hours. The reaction mixture was diluted with 0.1M HCl (10 mL) and extracted with DCM (3×10 mL). The combined organic portions were washed with a saturated solution of sodium bicarbonate (10 mL), brine (10 mL), water (10 mL) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-70% EtOAc/iso-hexane afforded the title compound.

후처리

  1. stirringThe reaction mixture was stirred for 20 hours
  2. extractionextracted with DCM (3×10 mL)
  3. washThe combined organic portions were washed with a saturated solution of sodium bicarbonate (10 mL), brine (10 mL), water (10 mL)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude product by chromatography on silica eluting with 0-70% EtOAc/iso-hexane

출처 및 근거

ORD 기록
ord-7e7f6546efd94f559d2185ce072fc959
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546416B2

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