Sodium borohydride → 3-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]phenyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-one

HRID 1026517Notes

Reaction equation

HRID 1026517 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[CH:34]=[CH:33][CH:32]=[C:31]([N:35]3[C:47](=[O:48])[C:46]4[S:45][C:44]5[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=5[C:38]=4[CH:37]=[N:36]3)[C:28]=2[CH:29]=[O:30])=[CH:3]1.[BH4-].[Na+]>CO>[OH:30][CH2:29][C:28]1[C:27]([C:4]2[CH:5]=[C:6]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19]([CH:22]5[CH2:25][O:24][CH2:23]5)[CH2:18][C@@H:17]4[CH3:26])=[CH:12][N:11]=3)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=2)=[CH:34][CH:33]=[CH:32][C:31]=1[N:35]1[C:47](=[O:48])[C:46]2[S:45][C:44]3[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=3[C:38]=2[CH:37]=[N:36]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866837782-[1-Methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxopyridin-3-yl]-6-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}benzaldehyde

Product 1

HCID 778447553-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]phenyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-oneYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

At 0° C., to a solution of 130b (120 mg, 0.18 mmol) in methanol (5 mL) was added sodium borohydride (20 mg, 0.54 mmol). The reaction was stirred for 30 minutes. It was then quenched with water (1 mL) and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 130 (70 mg, 59%). LCMS: [M+H]+ 666.3. 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J=2.0 Hz, 1H), 8.26 (s, 1H), 7.98 (s, 1H), 7.84 (s, 1H), 7.56-7.54 (m, 2H), 7.42 (d, J=2.5 Hz, 1H), 7.37 (dd, J=2.0, 7.0 Hz, 1H), 7.31 (d, J=8.0 Hz, 1H), 6.83 (d, J=8.5 Hz, 1H), 4.72-4.66 (m, 4H), 4.36 (d, J=5.0 Hz, 2H), 4.05 (t, J=5.5 Hz, 1H), 3.72 (s, 3H), 3.55-3.54 (m, 1H), 3.46-3.45 (m, 1H), 3.08-3.06 (m, 2H), 2.99 (t, J=5.0 Hz, 2H), 2.87 (t, J=5.0 Hz, 2H), 2.60-2.59 (m, 1H), 2.49-2.48 (m, 2H), 2.20-2.19 (m, 1H), 2.02-1.96 (m, 4H), 0.99 (d, J=6.0 Hz, 3H).

Workup

  1. customIt was then quenched with water (1 mL)
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-8c5e18b99b9841ca8da0b9a272e60a21
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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