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

HRID 1411906Notes

Reaction equation

HRID 1411906 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[C:22]([CH:23]=[O:24])=[C:21]([N:25]4[CH2:37][CH2:36][C:35]5[N:34]6[C:29]([CH2:30][CH2:31][CH2:32][CH2:33]6)=[CH:28][C:27]=5[C:26]4=[O:38])[N:20]=[CH:19][CH:18]=3)[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:18]=[CH:19][N:20]=[C:21]([N:25]4[CH2:37][CH2:36][C:35]5[N:34]6[C:29]([CH2:30][CH2:31][CH2:32][CH2:33]6)=[CH:28][C:27]=5[C:26]4=[O:38])[C:22]=3[CH2:23][OH:24])[CH:10]=2)=[N:3]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866844574-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

Product 1

HCID 715585472-[4-[5-[(1,5-Dimethylpyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-oneYield 67.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 242b (150 mg, 0.29 mmol, 1.0 eq.), NaBH4 (55 mg, 1.46 mmol, 5.0 eq.), and methanol (10 mL). The resulting mixture was stirred at room temperature for 20 min. It was then filtered and the filtrate was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 242 (100 mg, 66%) as a white solid. MS-ESI: [M+H]+ 514.3. 1H NMR (500 MHz, DMSO-d6) δ 8.47 (d, J=5.5 Hz, 1H), 8.04-8.03 (m, 2H), 7.42 (d, J=2.0 Hz, 1H), 7.30 (d, J=5.0 Hz, 1H), 6.05 (s, 1H), 5.90 (s, 1H), 4.87-4.85 (m, 1H), 4.43-4.35 (m, 2H), 4.18-4.12 (m, 1H), 3.98-3.93 (m, 1H), 3.84-3.78 (m, 2H), 3.59 (s, 3H), 3.58 (s, 3H), 3.06-2.92 (m, 2H), 2.75-2.68 (m, 2H), 2.18 (s, 3H), 1.94-1.92 (m, 2H), 1.79-1.73 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-fdf8da4b4473448990c827c6c632412a
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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