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Diisopropylethylamine → 3-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(piperidine-1-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl ester

HRID 2230321
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HRID 2230321 반응식
[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH2:30])[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[N:33]1([S:39](Cl)(=[O:41])=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C.C(Cl)(Cl)Cl.CCCCCC>[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH:30][S:39]([N:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)(=[O:41])=[O:40])[CH2:26][CH:27]([CH3:28])[CH3:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:3])([CH3:2])[CH3:4]
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참가 물질

9

반응물 3

HCID 81531DiisopropylethylamineHCID 11298344Piperidine-1-sulfonyl chlorideHCID 540817292-(2-Amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

생성물 1

HCID 700590143-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(piperidine-1-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl ester

시약·촉매·용매 5

HCID 14284
4-(Dimethylamino)pyridine
촉매
HCID 6212Chloroform용매
HCID 6228Dimethylformamide용매
HCID 8058Hexane용매
HCID 8857Ethyl Acetate용매

실험 절차

A solution of the product from Example AI ([S-(R*,R*)]-2-(2-amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester) (220 mg, 0.50 mmol), piperidinesulfonyl chloride (102 mg, 0.55 mmol, prepared by the method of Von Geldern, et al., J. Med. Chem., 1996;39:968-981), N,N-diisopropylethylamine (129 mg, 1.00 mmol), and DMAP (20 mg) in DMF (1 mL) is stirred at room temperature for 48 hours, diluted with ethyl acetate, and washed with water, 1N HCl, saturated NaHCO3 solution and brine, dried over anhydrous sodium sulfate, and concentrated. The remaining oily residue was purified via preparative TLC (50% EtOAc/hexane) giving a clear oil which was dissolved in 0.5 mL CHCl3, and diluted with 5 mL hexane. After 3 days at 3° C., the crystals that had formed were collected, and weighed 34 mg (12%), mp=125-126° C.

후처리

  1. washwashed with water, 1N HCl, saturated NaHCO3 solution and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe remaining oily residue was purified via preparative TLC (50% EtOAc/hexane)
  5. customgiving a clear oil which
  6. customthe crystals that had formed
  7. customwere collected

출처 및 근거

ORD 기록
ord-832e5db892434d47ab16a48717787b2f
출처 데이터셋
uspto-grants-2002_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06423689B1

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