Sodium borohydride → 3-[3-(Hydroxymethyl)-4-[1-methyl-5-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-4-one

HRID 1021908Notes

Reaction equation

HRID 1021908 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:18][CH2:17]3)=[CH:12][N:11]=2)=[CH:5][C:4]([C:26]2[C:31]([CH:32]=[O:33])=[C:30]([N:34]3[C:46](=[O:47])[C:38]4=[CH:39][N:40]5[C:45]([CH2:44][CH2:43][CH2:42][CH2:41]5)=[C:37]4[CH:36]=[N:35]3)[N:29]=[CH:28][CH:27]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:33][CH2:32][C:31]1[C:30]([N:34]2[C:46](=[O:47])[C:38]3=[CH:39][N:40]4[C:45]([CH2:44][CH2:43][CH2:42][CH2:41]4)=[C:37]3[CH:36]=[N:35]2)=[N:29][CH:28]=[CH:27][C:26]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:17][CH2:18][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:20][CH2:21]3)=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866843674-(1-Methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde

Product 1

HCID 715577533-[3-(Hydroxymethyl)-4-[1-methyl-5-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-4-oneYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 198a (80 mg, 0.13 mmol) in methanol (4 mL) was added NaBH4 (14 mg, 0.39 mmol). The mixture was stirred at 20° C. for 2 h. It was then evaporated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 198 (38 mg, 43%) as an off-white solid. MS-ESI: [M+H]+ 636.4. 1H NMR (500 MHz, DMSO-d6) δ 8.65 (d, J=2.0 Hz, 1H), 8.54 (d, J=5.0 Hz, 1H), 8.44 (s, 1H), 8.25 (s, 1H), 7.88 (d, J=2.5 Hz, 1H), 7.62 (s, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.46 (d, J=4.5 Hz, 1H), 7.39-7.36 (m, 1H), 7.25-7.23 (m, 1H), 4.67 (bs, 1H), 4.55 (t, J=6.5 Hz, 2H), 4.46 (t, J=6.0 Hz, 2H), 4.33-4.31 (m, 2H), 4.26-4.20 (m, 2H), 3.59 (s, 3H), 3.46-3.41 (m, 1H), 3.09-3.03 (m, 6H), 2.39-2.37 (m, 4H), 2.04-1.96 (m, 2H), 1.93-1.86 (m, 2H).

Workup

  1. customIt was then evaporated under reduced pressure
  2. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-fc88eb06552e485da5b0805a30d1d135
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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