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 1685361노트

반응식

HRID 1685361 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-074dc78fbed5466fb11bc03161b59f4f
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148400B2

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