Sodium borohydride → 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-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 592811Notes

Reaction equation

HRID 592811 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][C@@H:17]3[CH3:26])=[CH:12][N:11]=2)=[CH:5][C:4]([C:27]2[C:32]([CH:33]=[O:34])=[C:31]([N:35]3[C:47](=[O:48])[C:39]4=[CH:40][N:41]5[C:46]([CH2:45][CH2:44][CH2:43][CH2:42]5)=[C:38]4[CH:37]=[N:36]3)[N:30]=[CH:29][CH:28]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:34][CH2:33][C:32]1[C:31]([N:35]2[C:47](=[O:48])[C:39]3=[CH:40][N:41]4[C:46]([CH2:45][CH2:44][CH2:43][CH2:42]4)=[C:38]3[CH:37]=[N:36]2)=[N:30][CH:29]=[CH:28][C:27]=1[C:4]1[CH:5]=[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[CH2:23][O:24][CH2:25]4)[CH2:18][C@@H:17]3[CH3:26])=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86684353(S)-4-(1-Methyl-5-(5-(2-methyl-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 715575983-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-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 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 192d (160 mg, 0.25 mmol) in MeOH (20 mL) was added NaBH4 (28 mg, 0.75 mmol). The mixture was stirred at 20° C. for 2 h and evaporated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 192 (97 mg, 60%) as a yellow solid. MS-ESI: [M+H]+ 650.4. 1H NMR (500 MHz, DMSO-d6) δ 8.65 (d, J=2.5 Hz, 1H), 8.54 (d, J=4.5 Hz, 1H), 8.45 (s, 1H), 8.25 (s, 1H), 7.86 (d, J=2.5 Hz, 1H), 7.62 (s, 1H), 7.51 (d, J=2.5 Hz, 1H), 7.47 (d, J=5.0 Hz, 1H), 7.38-7.36 (m, 1H), 7.25 (d, J=9.5 Hz, 1H), 4.66 (s, 1H), 4.57-4.54 (m, 2H), 4.48-4.46 (m, 1H), 4.43-4.41 (m, 1H), 4.33 (s, 2H), 4.25-4.21 (m, 2H), 3.69-3.66 (m, 1H), 3.60 (s, 3H), 3.42-3.37 (m, 1H), 3.11-3.07 (m, 1H), 3.06-3.04 (m, 2H), 2.97-2.92 (m, 1H), 2.55-2.53 (m, 1H), 2.35-2.29 (m, 2H), 2.19-2.17 (m, 1H), 2.04-1.96 (m, 2H), 1.93-1.85 (m, 2H), 0.93 (d, J=6.5 Hz, 3H).

Workup

  1. customevaporated under reduced pressure
  2. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-4fd9c5e644684fa2ae3b71c1ab18096f
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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