(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide → (R)-5-(5-Cyano-1H-pyrrol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525688ノート

反応式

HRID 525688 の反応式
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].C(OC([N:35]1[C:39]([C:40]#[N:41])=[CH:38][CH:37]=[C:36]1B(O)O)=O)(C)(C)C>>[C:40]([C:39]1[NH:35][C:36]([C:2]2[C:3]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]3)=[N:4][CH:5]=[C:6]([CH:21]=2)[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:18])([F:19])[F:20])=[CH:12][CH:11]=2)=[O:8])=[CH:37][CH:38]=1)#[N:41]

参加物

3

反応物 2

HCID 86702593(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamideHCID 89907888(1-(tert-butoxycarbonyl)-5-cyano-1H-pyrrol-2-yl)boronic acid

生成物 1

HCID 89907035(R)-5-(5-Cyano-1H-pyrrol-2-yl)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

実験手順

The title compound was prepared in an analogous fashion to that described in Example 29 using (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.1) and (1-(tert-butoxycarbonyl)-5-cyano-1H-pyrrol-2-yl)boronic acid (Stage 29.1) to afford an off-white solid. UPLC-MS (Condition 3) tR=1.03 min, m/z=458.1[M+H]+, m/z=456.1 [M−H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.77 (m, J=6.48, 3.06 Hz, 1H) 1.82-1.92 (m, 1H) 2.95 (d, J=11.49 Hz, 1H) 3.26 (dd, J=11.74, 4.65 Hz, 1H) 3.31-3.34 (m, 1H) 3.40-3.50 (m, 1H) 4.19-4.28 (m, 1H) 4.88 (d, J=3.42 Hz, 1H) 6.31 (dd, J=3.67, 2.20 Hz, 1H) 7.01 (dd, J=3.67, 2.20 Hz, 1H) 7.34 (d, J=8.31 Hz, 2H) 7.82-7.89 (m, 2H) 8.07 (d, J=2.45 Hz, 1H) 8.76 (d, J=2.45 Hz, 1H) 10.16 (s, 1H) 12.59 (br. s, 1H).

後処理

  1. customto afford an off-white solid

出典と根拠

ORDレコード
ord-a67b99a22d3846ad934d80be5bacdf38
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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