Sodium borohydride → 3-{3'-Hydroxymethyl-1-methyl-5-[5-((R)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyridazin-4-one

HRID 1021764Notes

Reaction equation

HRID 1021764 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:32]=[CH:31][N:30]=[C:29]([N:33]3[C:45](=[O:46])[C:44]4[S:43][C:42]5[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=5[C:36]=4[CH:35]=[N:34]3)[C:28]=2[CH:47]=[O:48])=[CH:3]1.[BH4-].[Na+]>CO>[OH:48][CH2:47][C:28]1[C:29]([N:33]2[C:45](=[O:46])[C:44]3[S:43][C:42]4[CH2:41][CH2:40][CH2:39][CH2:38][C:37]=4[C:36]=3[CH:35]=[N:34]2)=[N:30][CH:31]=[CH:32][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 866842744-[1-Methyl-5-({5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde

Product 1

HCID 866842753-{3'-Hydroxymethyl-1-methyl-5-[5-((R)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyridazin-4-oneYield 19%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 154a (150 mg, 0.23 mmol), NaBH4 (35 mg, 0.92), and methanol (10 mL) was stirred at room temperature for 1 h. The mixture was then quenched with water (8 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 154 (29 mg, 19%). MS-ESI: [M+H]+ 667. 1H NMR (500 MHz, DMSO-d6) δ 8.64 (d, J=2.5 Hz, 1H), 8.56 (d, J=5.0 Hz, 1H), 8.49-8.47 (m, 2H), 7.85 (d, J=3.0 Hz, 1H), 7.53 (d, J=5.0 Hz, 1H), 7.48 (d, J=2.5 Hz, 1H), 7.38-7.36 (m, 1H), 7.24 (d, J=8.5 Hz, 1H), 4.85 (t, J=9.5 Hz, 1H), 4.57-4.54 (m, 2H), 4.43-4.36 (m, 4H), 3.69-3.68 (m, 1H), 3.60 (s, 3H), 3.40-3.36 (m, 1H), 3.11-3.07 (m, 1H), 2.97-2.86 (m, 6H), 2.33-2.31 (m, 2H), 2.16 (t, J=8.5 Hz, 1H), 1.89-1.86 (m, 4H), 0.92 (d, J=6.5 Hz, 3H).

Workup

  1. customThe mixture was then quenched with water (8 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (2×10 mL)
  4. extractionThe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-bd5953770299411dae8a62d1f28b293c
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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