Piperidine-3-carbonitrile → N-(7-(3-cyanopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1409158

反応式

HRID 1409158 の反応式
Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[NH:24]1[CH2:29][CH2:28][CH2:27][CH:26]([C:30]#[N:31])[CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[C:30]([CH:26]1[CH2:27][CH2:28][CH2:29][N:24]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[CH:3]=2)[CH2:25]1)#[N:31]

参加物

6

反応物 2

HCID 420926Piperidine-3-carbonitrileHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

生成物 1

HCID 68397586N-(7-(3-cyanopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide収率 85.1%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide触媒HCID 887Methanol溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol) and piperidine-3-carbonitrile (33 mg, 0.302 mmol) in NMP (0.950 mL) was stirred at 85° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 35-60% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a orange solid (52 mg, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 1.73-2.11 (m, 4H) 3.25-3.34 (m, 1H) 3.53-3.63 (m, 1H) 3.68-3.79 (m, 1H) 3.98 (dd, J=12.51, 2.65 Hz, 1H) 4.12-4.23 (m, 1H) 6.38 (d, J=2.27 Hz, 1H) 7.46 (s, 1H) 7.60 (d, J=8.59 Hz, 2H) 8.00 (d, J=8.59 Hz, 2H) 8.12 (d, J=2.27 Hz, 1H) 10.93 (s, 1H). ESI-MS: m/z 405.3 (M+H)+.

後処理

  1. customwas then purified by preparatory HPLC, 35-60% (MeCN/H2O gradient+0.01% TFA)

出典と根拠

ORDレコード
ord-6e468e60299a49f299186f9cafa6a98c
出典データセット
uspto-grants-2014_12
特許番号
US08921358B2

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