4-Methylmorpholine → (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

HRID 1620943노트

반응식

HRID 1620943 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:16][C@@H:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:18]([OH:20])=O)[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:41][CH2:42][C:43]#[N:44].P(O)([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[C:42]([CH2:43][NH:44][C:18](=[O:20])[C@@H:17]([NH:16][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])#[N:41]

참가 물질

8

반응물 5

HCID 79724-Methylmorpholine2회HCID 24203Sodium Phosphate, DibasicHCID 62365Isobutyl chloroformateHCID 11491918Aminoacetonitrile hydrochlorideHCID 67298368HCID 67298368, 화합물

생성물 1

HCID 86590549(2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid (1.17 g, 2.86 mmol) in THF (20 mL) at −10° C. were added 4-methylmorpholine (0.315 mL, 2.86 mmol) and isobutyl chloroformate (0.371 mL, 2.86 mmol). The reaction mixture was stirred for 10 minutes, whereupon aminoacetonitrile hydrochloride (0.318 g, 3.43 mmol) was added, followed by 4-methylmorpholine (0.315 mL, 2.86 mmol). The solution was stirred for 90 minutes. Ethyl acetate (30 mL) and aqueous disodium phosphate (30 mL) were added. The organic phase was separated, washed with brine, dried over MgSO4, and evaporated to dryness. The product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide.

후처리

  1. additionwas added
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution)

출처 및 근거

ORD 기록
ord-80b816ccb9e54bc0b87a2025374aea4d
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772336B2

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