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 1455605ノート

反応式

HRID 1455605 の反応式
[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

参加物

7

反応物 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

生成物 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)-amide収率 75%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c0c33300fd8f4740a0e62b5e40a25f39
出典データセット
uspto-grants-2009_01
特許番号
US07482448B2

反応ノート

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