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 592969Notes

Reaction equation

HRID 592969 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-74387ad25b3e49619f77e834ba4c6d61
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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