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

HRID 1022084Notes

Reaction equation

HRID 1022084 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:14](=[O:15])[N:13]([CH3:16])[CH:12]=[C:11]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([N:23]4[CH2:35][CH2:34][C:33]5[N:32]6[C:27]([CH2:28][CH2:29][CH2:30][CH2:31]6)=[C:26]([F:36])[C:25]=5[C:24]4=[O:37])[C:18]=3[CH:38]=[O:39])[CH:10]=2)=[N:3]1.[BH4-].[Na+]>CO>[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:14](=[O:15])[N:13]([CH3:16])[CH:12]=[C:11]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([N:23]4[CH2:35][CH2:34][C:33]5[N:32]6[C:27]([CH2:28][CH2:29][CH2:30][CH2:31]6)=[C:26]([F:36])[C:25]=5[C:24]4=[O:37])[C:18]=3[CH2:38][OH:39])[CH:10]=2)=[N:3]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866844934-{5-[(1,5-Dimethyl-1H-pyrazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydro pyridin-3-yl}-2-{10-fluoro-1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrido[3,4-b]indolizin-2-yl}pyridine-3-carbaldehyde

Product 1

HCID 866844942-[4-[5-[(1,5-Dimethylpyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-10-fluoro-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-oneYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 261a (90.0 mg, 0.17 mmol) in methanol (5 mL) was added sodium borohydride (64.6 mg, 1.7 mmol) at room temperature. The reaction was stirred for 0.5 h. It was then quenched with water (2 mL) and evaporated in vacuo. The residue was extracted with dichloromethane (3×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 261 (47.0 mg, 52%) as a white solid. MS-ESI: [M+H]+ 532.3. 1H NMR (500 MHz, DMSO-d6) δ 8.47 (d, J=5.0 Hz, 1H), 8.05 (s, 1H), 8.03 (d, J=2.5 Hz, 1H), 7.39 (d, J=2.5 Hz, 1H), 7.31 (d, J=5.0 Hz, 1H), 5.89 (s, 1H), 4.87-4.85 (m, 1H), 4.45-4.36 (m, 2H), 4.11-4.09 (m, 1H), 3.93-3.91 (m, 1H), 3.79-3.76 (m, 2H), 3.59 (s, 3H), 3.58 (s, 3H), 3.00-2.94 (m, 2H), 2.66-2.63 (m, 2H), 2.18 (s, 3H), 1.90-1.88 (m, 2H), 1.78-1.73 (m, 2H)

Workup

  1. customIt was then quenched with water (2 mL)
  2. customevaporated in vacuo
  3. extractionThe residue was extracted with dichloromethane (3×10 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-7d7dd228d6d642a3a44c9640bdd49fc3
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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