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 407625노트

반응식

HRID 407625 반응식
[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]

참가 물질

4

반응물 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

생성물 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)-one수율 49.5%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-62dd05a20c3649a793ecd7ef8d45003b
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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