1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(2-hydroxy-2,2-diphenylethyl)-4-(2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinamide

HRID 1685361ノート

反応式

HRID 1685361 の反応式
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([CH3:16])[N:13]=[C:12]([NH:17][C:18]3[S:19][C:20]([S:23][C:24]4[CH:29]=[CH:28][N:27]=[C:26]([C:30]([OH:32])=O)[CH:25]=4)=[CH:21][N:22]=3)[CH:11]=2)[CH2:6][CH2:5]1.[NH2:33][CH2:34][C:35]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[OH:36].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[OH:36][C:35]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:34][NH:33][C:30](=[O:32])[C:26]1[CH:25]=[C:24]([S:23][C:20]2[S:19][C:18]([NH:17][C:12]3[CH:11]=[C:10]([N:7]4[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6]4)[N:15]=[C:14]([CH3:16])[N:13]=3)=[N:22][CH:21]=2)[CH:29]=[CH:28][N:27]=1

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2018282-Amino-1,1-diphenylethanolHCID 592004034-(2-(6-(4-(2-Hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinic acid

生成物 1

HCID 59200421N-(2-hydroxy-2,2-diphenylethyl)-4-(2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinamide収率 44%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

To a solution of 4-(2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinic acid (43.2 mg, 0.0912 mmol) and 2-amino-1,1-diphenylethanol (30.8 mg, 0.144 mmol, described in Synthesis of amines, Example D) in NMP (3 mL) was added HOBT (12.3 mg, 0.0910 mmol), EDAC (27.4 mg, 0.143 mmol) and diisopropylethylamine (0.05 mL, 0.281 mmol). The reaction was stiffed at 23° C. overnight and was purified on Prep HPLC (water/acetonitrile/ammonium acetate) to give the title material (26.7 mgs, 44%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 10.51 (1H, s), 8.35-8.42 (2H, m), 7.75 (s, 1H), 7.62 (1H, d, J=1.26 Hz), 7.43 (5H, d, J=7.07 Hz), 7.34 (1H, dd, J=5.31, 2.02 Hz), 7.27 (5H, t, J=7.71 Hz), 7.16 2H, t, J=7.33 Hz), 6.30 (1H, s), 6.03 (1H, s), 4.45 (1H, t, J=5.18 Hz), 4.09 (2H, d, J=5.56 Hz), 3.50 (7H, s), 2.41 (3H, t, J=6.32 Hz), 2.33 (3H, s). LC/MS (M+H)+: 669. HPLC ret. time (Condition E): 1.84 min. HRMS calcd: 669.2430; found: 669.2434.

後処理

  1. customwas purified on Prep HPLC (water/acetonitrile/ammonium acetate)

出典と根拠

ORDレコード
ord-074dc78fbed5466fb11bc03161b59f4f
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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