Sodium borohydride → 10-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-one

HRID 592967Notes

Reaction equation

HRID 592967 reaction equation
[F:1][C:2]1[C:3]2[C:14](=[O:15])[N:13]([C:16]3[C:21]([CH:22]=[O:23])=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:40]=[C:34]6[CH2:35][N:36]([CH3:39])[CH2:37][CH2:38][N:33]6[N:32]=5)[C:27](=[O:41])[N:26]([CH3:42])[CH:25]=4)[CH:19]=[CH:18][N:17]=3)[CH2:12][CH2:11][C:4]=2[N:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][CH2:6]2.[BH4-].[Na+]>CO>[F:1][C:2]1[C:3]2[C:14](=[O:15])[N:13]([C:16]3[C:21]([CH2:22][OH:23])=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:40]=[C:34]6[CH2:35][N:36]([CH3:39])[CH2:37][CH2:38][N:33]6[N:32]=5)[C:27](=[O:41])[N:26]([CH3:42])[CH:25]=4)[CH:19]=[CH:18][N:17]=3)[CH2:12][CH2:11][C:4]=2[N:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][CH2:6]2

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866844562-{10-Fluoro-1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrido[3,4-b]indolizin-2-yl}-4-[1-methyl-5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde

Product 1

HCID 7155839910-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-oneYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
12.5 °C

Procedure

To the solution of 241a (54.0 mg, 0.095 mmol) in methanol (5 mL) was added sodium borohydride (28.9 mg, 0.76 mmol) at 0° C. The reaction was stirred at 0-25° C. for 1.5 h. It was then quenched with water (5 mL). The mixture was evaporated under reduced pressure and the residue was extracted with dichloromethane (3×30 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 241 (8.0 mg, 15%) as a white solid. MS-ESI: [M+H]+ 573.3. 1H NMR (500 MHz, DMSO-d6) δ 8.47 (d, J=5.0 Hz, 1H), 8.21 (s, 1H), 8.06 (d, J=2.0 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.31 (d, J=5.0 Hz, 1H), 5.88 (s, 1H), 4.87-4.85 (m, 1H), 4.44-4.35 (m, 2H), 4.13-4.08 (m, 1H), 3.92-3.89 (m, 3H), 3.79-3.76 (m, 2H), 3.58 (s, 3H), 3.49 (s, 2H), 2.99-2.94 (m, 2H), 2.79-2.77 (m, 2H), 2.66-2.64 (m, 2H), 2.35 (s, 3H), 1.90-1.78 (m, 2H), 1.75-1.73 (m, 2H).

Workup

  1. customIt was then quenched with water (5 mL)
  2. customThe mixture was evaporated under reduced pressure
  3. extractionthe residue was extracted with dichloromethane (3×30 mL)
  4. extractionThe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-e3b6567de4334dd5b2681ecb2aa379d6
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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