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Methanol → 4-Hydroxymethyl-3-[1-methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridine-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde

HRID 592544
Notes
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Reaction equation

HRID 592544 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[CH:27]=[N:28][CH:29]=[C:30]([N:34]3[CH2:45][CH2:44][C:43]4[C:42]5[CH2:41][C:40]([CH3:47])([CH3:46])[CH2:39][C:38]=5[S:37][C:36]=4[C:35]3=[O:48])[C:31]=2[CH:32]=[O:33])=[CH:3]1.[BH4-].[Na+].[CH3:51][OH:52]>>[OH:33][CH2:32][C:31]1([CH:51]=[O:52])[C:30]([N:34]2[CH2:45][CH2:44][C:43]3[C:42]4[CH2:41][C:40]([CH3:46])([CH3:47])[CH2:39][C:38]=4[S:37][C:36]=3[C:35]2=[O:48])=[CH:29][N:28]=[CH:27][CH: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[CH2:23][O:24][CH2:25]4)[CH2:20][CH2:21]3)=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 866841783-[1-Methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridine-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde

Product 1

HCID 86684179
4-Hydroxymethyl-3-[1-methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridine-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde
Yield 45%

Procedure

To a solution of 106j (130 mg, 0.20 mmol) in methanol (5 mL) at 0° C. was added sodium borohydride (22 mg, 0.6 mmol) and stirred for 30 minutes. Then the reaction mixture was quenched with water (1.0 mL) and concentrated. The residue was purified by reverse-phase prep-HPLC to afford 106 (60 mg, 45%) as a yellow solid. LCMS: [M+H]+ : 668. 1H NMR (500 MHz, DMSO) δ 8.58 (d, J=2.0, 1H), 8.56 (s, 1H), 8.49 (s, 1H), 8.41 (s, 1H), 7.87 (d, J=2.5, 1H), 7.38-7.36 (m, 2H), 7.24-7.22 (m, 1H), 5.15 (t, J=5.0, 1H), 4.56-4.42 (m, 6H), 4.08-4.04 (m, 2H), 3.60 (s, 3H), 3.43-3.42 (m, 1H), 3.07-2.94 (m, 6H), 2.55-2.53 (m, 4H), 2.39-2.38 (m, 4H), 1.23 (s, 6H)

Workup

  1. customThen the reaction mixture was quenched with water (1.0 mL)
  2. concentrationconcentrated
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-221670b428de4efd8dff36019bca3e0b
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09238655B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes