Sodium borohydride → (R)-6-tert-Butyl-8-fluoro-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)phthalazin-1(2H)-one

HRID 1185041ノート

反応式

HRID 1185041 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[CH:38]=[CH:37][C:36]([N:39]5[CH2:44][CH2:43][N:42]([CH:45]6[CH2:48][O:47][CH2:46]6)[CH2:41][C@H:40]5[CH3:49])=[CH:35][N:34]=4)[C:29](=[O:50])[N:28]([CH3:51])[CH:27]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[CH:38]=[CH:37][C:36]([N:39]5[CH2:44][CH2:43][N:42]([CH:45]6[CH2:46][O:47][CH2:48]6)[CH2:41][C@H:40]5[CH3:49])=[CH:35][N:34]=4)[C:29](=[O:50])[N:28]([CH3:51])[CH:27]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:2])([CH3:3])[CH3:4]

参加物

4

反応物 2

HCID 4311764Sodium borohydrideHCID 86683921(R)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-fluoro-6-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydro-pyridin-3-yl)benzaldehyde

生成物 1

HCID 86683922(R)-6-tert-Butyl-8-fluoro-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)phthalazin-1(2H)-one収率 49.5%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 107a (77 mg, 1.0 eq., 0.11 mmol), NaBH4 (21 mg, 5.0 eq., 0.55 mmol), and MeOH (10 mL). The mixture was stirred at room temperature for 1 h. It was then filtered and the filtrate was concentrated. The residue was purified by reverse-phase prep-HPLC to afford 107 (38 mg, 49%). MS: [M+H]+ 698.3. 1H NMR (500 MHz, CDCl3) δ 8.59 (d, J=2.0 Hz, 1H), 8.29 (d, J=2.5 Hz, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.81 (s, 1H), 7.56-7.54 (m, 2H), 7.40 (s, 1H), 7.31-7.27 (m, 2H), 7.11-7.10 (m, 1H), 6.81 (d, J=9.0 Hz, 1H), 4.71-4.62 (m, 4H), 4.35 (s, 2H), 3.73-3.70 (m, 4H), 3.53-3.46 (m, 2H), 3.08 (t, J=5.0 Hz, 2H), 2.56-2.46 (m, 3H), 2.22-2.18 (m, 1H), 1.43 (s, 9H), 0.98 (d, J=6.5 Hz, 3H).

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. filtrationIt was then filtered
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by reverse-phase prep-HPLC

出典と根拠

ORDレコード
ord-bd915cfd83004bc5a44c000cc12b2244
出典データセット
uspto-grants-2014_03
特許番号
US08669251B2

反応ノート

読み込み中…