Diisopropylethylamine → N4-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-[(S)-1-(4-fluoro-phenyl)-ethyl]-pyridine-2,4-diamine

反応式

[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3N=C(N[C@H](C4C=CC(F)=CC=4)C)C(CNC(=O)C)=[CH:12][C:11]=3F)[CH:5]=2)[CH2:3][CH2:2]1.[CH3:32][CH2:33][N:34](C(C)C)C(C)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([C@@H:48]([NH2:50])[CH3:49])=[CH:44][CH:43]=1>>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[CH:11]=[CH:12][N:34]=[C:33]([NH:50][C@H:48]([C:45]4[CH:46]=[CH:47][C:42]([F:41])=[CH:43][CH:44]=4)[CH3:49])[CH:32]=3)[CH:5]=2)[CH2:2][CH2:3]1

参加物

反応物 3

HCID 81531Diisopropylethylamine

HCID 2779063(S)-1-(4-Fluorophenyl)-ethylamine

HCID 67460058(S)-N-((6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)pyridin-3-yl)methyl)acetamide

生成物 1

HCID 86620605N4-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-[(S)-1-(4-fluoro-phenyl)-ethyl]-pyridine-2,4-diamine

反応条件

温度: 160 °C

実験手順

A mixture of (2-chloro-pyridin-4-yl)-(5-cyclopropyl-1H-pyrazole-3-yl)-amine (Method 4; 0.116 g, 0.49 mmol), DIEA (0.20 ml, 1.18 mmol), and (S)-1-(4-fluoro-phenyl)-ethylamine (1.0 ml, 7.4 mmol) was heated to 160° C. in a sealed tube for 2 days. The reaction mixture was concentrated under reduced pressure and purified by reverse-phase prep HPLC (column: mC-PACK-ODS-AQ, 250×20 nm, 3.0×50 mm; 5-95% gradient MeCN (0.05% TFA) in water (0.1% TFA); flow rate: 10.0 ml/min). 1H NMR (400 MHz) δ 0.696 (m, 2H), 0.958 (m, 2H), 1.49 (m, 4H), 4.75 (q, 1H), 5.60 (s, 1H), 7.19 (t, 2H), 7.29 (t, 1H), 7.42 (t, 3H), 7.6 (s, 1H), 9.89 (s, 1H). MS: Calcd.: 337. Found: [M+H]+ 338.

後処理

concentrationThe reaction mixture was concentrated under reduced pressure
custompurified by reverse-phase prep HPLC (column: mC-PACK-ODS-AQ, 250×20 nm, 3.0×50 mm; 5-95% gradient MeCN (0.05% TFA) in water (0.1% TFA); flow rate: 10.0 ml/min)

出典と根拠

ORDレコード: ord-4a3a8f6b5d5a40b286da03c8be90d033
出典データセット: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US08835465B2

反応ノート

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