Sodium borohydride → 6-tert-butyl-2-[4-[5-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 407715노트

반응식

HRID 407715 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[N:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:40]=[C:35]5[CH2:36][O:37][CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:41])[N:27]([CH3:42])[CH:26]=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[C:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:40]=[C:35]5[CH2:36][O:37][CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:41])[N:27]([CH3:42])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

참가 물질

4

반응물 2

HCID 4311764Sodium borohydrideHCID 866839832-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

생성물 1

HCID 866839846-tert-butyl-2-[4-[5-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one수율 47.1%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 131e (220 mg, 1.0 eq., 0.39 mmol), NaBH4 (73 mg, 5.0 eq., 1.90 mmol), and methanol (10 mL). The mixture was stirred at room temperature for 1 h and quenched with water (5 mL). It was then concentrated under reduced pressure and resulting residue was extracted with dichloromethane (3×10 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 131 (105 mg, 47%). MS-ESI: [M+H]+ 571.8. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=5.0 Hz, 1H), 8.35 (d, J=2.5 Hz, 1H), 8.03 (d, J=2.5 Hz, 1H), 7.59-7.53 (m, 4H), 7.48 (s, 1H), 5.73 (s, 1H), 4.81 (s, 2H), 4.51 (bs, 2H), 4.12-4.05 (m, overlap, 5H), 3.73 (s, 3H), 1.46 (s, 9H).

후처리

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customquenched with water (5 mL)
  3. concentrationIt was then concentrated under reduced pressure
  4. customresulting residue
  5. extractionwas extracted with dichloromethane (3×10 mL)
  6. concentrationThe combined organic layer was concentrated under reduced pressure
  7. customthe residue was purified by reverse-phase prep-HPLC

출처 및 근거

ORD 기록
ord-dbd51347e6f74d7283c0f642ab930106
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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