1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-(4-(5-(5-amino-6-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone

HRID 1749693ノート

反応式

HRID 1749693 の反応式
[C:1]([C:5]1[O:9][C:8]([C:10]2[C:11]([NH2:29])=[N:12][CH:13]=[C:14]([C:16]3[N:20]([CH2:21][CH3:22])[N:19]=[C:18]([CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[N:17]=3)[N:15]=2)=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:30][C:31]1([CH3:39])[O:35][C@H:34]([C:36]([O-])=[O:37])[CH2:33][O:32]1.[K+].CCN=C=NCCCN(C)C.O.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[NH2:29][C:11]1[N:12]=[CH:13][C:14]([C:16]2[N:20]([CH2:21][CH3:22])[N:19]=[C:18]([CH:23]3[CH2:28][CH2:27][N:26]([C:36]([C@@H:34]4[CH2:33][O:32][C:31]([CH3:39])([CH3:30])[O:35]4)=[O:37])[CH2:25][CH2:24]3)[N:17]=2)=[N:15][C:10]=1[C:8]1[O:9][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[N:6][N:7]=1

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 23678351potassium (4S)-2,2-dimethyl-1,3-dioxolane-4-carboxylateHCID 86727668HCID 86727668、化合物

生成物 1

HCID 86727675(S)-(4-(5-(5-amino-6-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone収率 121.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 3-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)-5-(1-ethyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine (257 mg, 0.50 mmol, TFA salt), potassium (S)-2,2-dimethyl-1,3-dioxolane-4-carboxylate (101 mg, 0.55 mmol) and EDCI (105 mg, 0.55 mmol) in DCM (5 mL) were added 1-hydroxy-1H-benzotriazol hydrate (85 mg, 0.56 mmol) and DIPEA (194 mg, 1.50 mmol). The mixture was stirred for 16 hours at room temperature. Water was added to the mixture and the mixture was extracted with DCM. The organic layers were washed with brine and dried over Na2SO4, filtered and concentrated to give (S)-(4-(5-(5-amino-6-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone (320 mg). Mass Spectrum [M+H]+=526. To a mixture of (S)-(4-(5-(5-amino-6-(5-(tert-butyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone (320 mg) in DCM (10 mL) at r.t was added dropwise TFA (1.6 ml, 20.77 mmol). The mixture was stirred for 16 h at r.t, concentrated and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length) using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as the eluant. The fractions containing the desired compound were evaporated to dryness to afford the title compound (142 mg, 48%) as a white solid. 1H NMR Spectrum (400 Hz, DMSO-d6, 30° C.): 1.45 (12H, m), 1.56 (1H, m), 1.70 (1H, m), 1.98 (2H, m), 2.85 (1H, m), 3.00 (1H, m), 3.20 (1H, m), 3.45 (1H, s), 3.55 (1H, s), 4.05 (1H, m), 4.35 (2H, m), 4.60 (2H, m), 4.70 (1H, m), 4.85 (1H, m), 7.90 (2H, m), 8.85 (1H, s); Mass Spectrum [M+H]+=486.

後処理

  1. extractionthe mixture was extracted with DCM
  2. washThe organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-539d31e413c04b3fad63011c6e5e20c2
出典データセット
uspto-grants-2015_10
特許番号
US09156831B2

反応ノート

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