Diisopropylethylamine → Perhydro-1, 4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide

HRID 1455605노트

반응식

HRID 1455605 반응식
[F:1][C:2]([F:19])([CH3:18])[CH2:3][C@H:4]([NH:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10])[C:5]([OH:7])=O.Cl.[NH2:21][CH:22]([CH2:33][CH3:34])[C@@H:23]([C:25]1[O:29][N:28]=[C:27]([CH:30]2[CH2:32][CH2:31]2)[N:26]=1)[OH:24].C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl>[CH:30]1([C:27]2[N:26]=[C:25]([CH:23]([OH:24])[C@@H:22]([NH:21][C:5]([C@@H:4]([NH:8][C:9]([N:11]3[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[O:10])[CH2:3][C:2]([F:1])([F:19])[CH3:18])=[O:7])[CH2:33][CH3:34])[O:29][N:28]=2)[CH2:31][CH2:32]1

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57535332(S)-4,4-Difluoro-2-[(perhydro-1,4-oxazepine-4-carbonyl)-amino]-pentanoic acidHCID 68820971(S)-2-amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-butan-1-ol hydrochloride

생성물 1

HCID 86607352Perhydro-1, 4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide수율 75%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a mixture of (S)-4,4-Difluoro-2-[(perhydro-1,4-oxazepine-4-carbonyl)-amino]-pentanoic acid (97 mg, 0.35 mmol), (S)-2-Amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-butan-1-ol hydrochloride (83 mg, 0.36 mmol) and diisopropylethyl amine (121 μL, 0.70 mmol) in dry dichloromethane (12 mL) is added 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (66 mg, 0.35 mmol) and 1-hydroxybenzotriazole hydrate (47 mg, 0.35 mmol). The mixture is stirred at room temperature for 16 hr then is diluted with dichloromethane (20 mL) and washed with dilute HCl (30 mL), then saturated NaHCO3 (30 mL). The organic layer is dried (Na2SO4) and concentrated in vacuum. The residue is purified over 12 g silica gel, eluting with ethyl acetate: heptane (gradient 50-100%) to afford Perhydro-1,4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide (120 mg, 75%) as a glassy solid. LC/MS 100% 460 (M+H).

후처리

  1. washwashed with dilute HCl (30 mL)
  2. dry with materialThe organic layer is dried (Na2SO4)
  3. concentrationconcentrated in vacuum
  4. customThe residue is purified over 12 g silica gel
  5. washeluting with ethyl acetate

출처 및 근거

ORD 기록
ord-c0c33300fd8f4740a0e62b5e40a25f39
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482448B2

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