1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl (6-(5-(3-fluoro-2-(2-hydroxy-2-phenylpentylcarbamoyl)pyridin-4-ylthio)thiazol-2-ylamino)pyridin-3-yl)methyl(methyl)carbamate

HRID 1685356ノート

反応式

HRID 1685356 の反応式
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]2[S:19][C:20]([S:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:30]([OH:32])=O)[C:25]=3[F:33])=[CH:21][N:22]=2)=[N:15][CH:16]=1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:34][CH2:35][C:36]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([OH:40])[CH2:37][CH2:38][CH3:39].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[F:33][C:25]1[C:26]([C:30](=[O:32])[NH:34][CH2:35][C:36]([OH:40])([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:37][CH2:38][CH3:39])=[N:27][CH:28]=[CH:29][C:24]=1[S:23][C:20]1[S:19][C:18]([NH:17][C:14]2[N:15]=[CH:16][C:11]([CH2:10][N:8]([CH3:9])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:12][CH:13]=2)=[N:22][CH:21]=1

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 229923231-Amino-2-phenylpentan-2-olHCID 592004604-(2-(5-((Tert-butoxycarbonyl(methyl)amino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinic acid

生成物 1

HCID 59200485Tert-butyl (6-(5-(3-fluoro-2-(2-hydroxy-2-phenylpentylcarbamoyl)pyridin-4-ylthio)thiazol-2-ylamino)pyridin-3-yl)methyl(methyl)carbamate収率 61%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
23 °C

実験手順

To a solution of 4-(2-(5-((tert-butoxycarbonyl(methyl)amino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinic acid (120 mg, 0.244 mmol) and 1-amino-2-phenylpentan-2-ol (1.3 eq, 0.317 mmol, 57 mg) in NMP (4 mL) was added HOBT (1.3 eq, 0.317 mmol, 43 mg), EDAC (2 eq, 0.488 mmol, 94 mg) and diisopropylethylamine (5 eq, 1.22 mmol, 157 mg, 213 uL). The reaction was stirred at 23° C. overnight. The product was precipitated by addition of water to the reaction mixture. The solid was isolated by filtration to give the crude title material (97 mg, 61%) as a solid which was used as such in the next reaction. 1H NMR (400 MHz, DMSO-d6) δ ppm: 0.76 (3H, t, J=7.33 Hz), 0.90 (1H, m), 1.18-1.32 (1H, m), 1.41 (9H, s), 1.65-1.84 (2H, m), 2.75 (3H, s), 3.62 (2H, d, J=5.81 Hz), 4.32 (2H, s) 7.04 (1H, t, J=5.18 Hz), 7.11 (1H, d, J=8.59 Hz), 7.20 (1H, t, J=7.33 Hz), 7.31 (2H, t, J=7.71 Hz), 7.44 (2H, d, J=7.33 Hz), 7.66 (1H, s), 7.82 (1H, s), 8.13-8.32 (3H, m), 11.93 (1H, s). LC/MS (M+H)+: 653. Ret. time: 2.257 (Condition A).

後処理

  1. customThe product was precipitated by addition of water to the reaction mixture
  2. customThe solid was isolated by filtration

出典と根拠

ORDレコード
ord-0d9f44dc1879447e8532806f70163384
出典データセット
uspto-grants-2012_04
特許番号
US08148400B2

反応ノート

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