Sodium borohydride → 2-[5-fluoro-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-tetrahydropyridazino[4,5-b]indolizin-1-one

HRID 519394Notes

Reaction equation

HRID 519394 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([N:10]2[C:22](=[O:23])[C:14]3[CH:15]=[C:16]4[N:21]([C:13]=3[CH:12]=[N:11]2)[CH2:20][CH2:19][CH2:18][CH2:17]4)[C:5]([CH:6]=[O:7])=[C:4]([C:24]2[CH:29]=[C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH:43]5[CH2:46][O:45][CH2:44]5)[CH2:39][CH:38]4[CH3:47])=[CH:33][N:32]=3)[C:27](=[O:48])[N:26]([CH3:49])[CH:25]=2)[CH:3]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([C:24]2[CH:29]=[C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH:43]5[CH2:44][O:45][CH2:46]5)[CH2:39][C@@H:38]4[CH3:47])=[CH:33][N:32]=3)[C:27](=[O:48])[N:26]([CH3:49])[CH:25]=2)[C:5]([CH2:6][OH:7])=[C:8]([N:10]2[C:22](=[O:23])[C:14]3[CH:15]=[C:16]4[N:21]([C:13]=3[CH:12]=[N:11]2)[CH2:20][CH2:19][CH2:18][CH2:17]4)[CH:9]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866837714-Fluoro-2-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-6,7,8,9-tetrahydropyridazino[4,5-b]indolizin-2(1H)-yl)benzaldehyde

Product 1

HCID 778447052-[5-fluoro-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-tetrahydropyridazino[4,5-b]indolizin-1-oneYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 127g (100.0 mg, 0.15 mmol) in methanol (20 mL) was added NaBH4 (17.0 mg, 0.45 mmol). The mixture was stirred at room temperature for 2 h. It was then quenched with water (1 mL) and the mixture was evaporated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 127 (56 mg, yield 56%) as a white solid. MS: [M+H]+ 667.4. 1H NMR (500 MHz, DMSO-d6) δ 8.58 (d, J=2.0, 1H), 8.47 (s, 1H), 8.40 (s, 1H), 7.85 (d, J=2.5, 1H), 7.39 (d, J=2.0, 1H), 7.37-7.34 (m, 1H), 7.30-7.28 (m, 1H), 7.25-7.22 (m, 2H), 6.48 (s, 1H), 4.57-4.53 (m, 2H), 4.46 (m, 2H), 4.41 (m, 1H), 4.25 (m, 2H), 4.20 (s, 2H), 3.69-3.64 (m, 1H), 3.58 (s, 3H), 3.41-3.36 (m, 1H), 3.10-3.07 (m, 1H), 2.96-2.92 (m, 3H), 2.54-2.50 (m, 1H), 2.35-2.28 (m, 2H), 2.18 (m, 1H), 2.04-2.00 (m, 2H), 1.87-1.82 (m, 2H), 0.92 (d, J=6.0, 3H).

Workup

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

Sources & evidence

ORD record
ord-0829497cf503415db4099dbb60c84751
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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