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

HRID 1411922Notes

Reaction equation

HRID 1411922 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[CH:37]=[CH: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[CH:37]=[CH: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 866844694-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

Product 1

HCID 866844702-[4-[5-[(1,5-Dimethylpyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-1-oneYield 48%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 246a (38 mg, 0.074 mmol, 1.0 eq.), NaBH4 (29 mg, 0.37 mmol, 5.0 eq.), and methanol (5 mL). The resulting mixture was stirred at room temperature for 20 min. It was then filtered and the filtrate was concentrated. The residue was purified by reverse-phase prep-HPLC to afford the title compound (18 mg, 48%) as a white solid. MS-ESI: [M+H]+ 512.3. 1H NMR (500 MHz, CDCl3) δ 8.58 (d, J=5.0 Hz, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.78 (d, J=2.5 Hz, 1H), 7.52 (d, J=5.0 Hz, 1H), 7.37 (s, 1H), 7.17 (d, J=7.0 Hz, 1H), 6.58-6.57 (m, 2H), 5.74 (s, 1H), 5.41-5.39 (m, 1H), 4.42-4.32 (m, 2H), 4.08 (t, J=6.5 Hz, 2H), 3.72 (s, 3H), 3.70 (s, 3H), 2.98 (t, J=6.5 Hz, 2H), 2.25 (s, 3H), 2.13-2.09 (m, 2H), 1.97-1.92 (m, 2H).

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. filtrationIt was then filtered
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-c9635796a89b4da58c3fc03020cca399
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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