Sodium borohydride → 3-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-one

HRID 592896Notes

Reaction equation

HRID 592896 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[S:11][C:12]3[CH2:13][N:14]([CH3:19])[CH2:15][CH2:16][C:17]=3[N:18]=2)=[CH:5][C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([N:26]3[C:38](=[O:39])[C:37]4[S:36][C:35]5[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=5[C:29]=4[CH:28]=[N:27]3)[C:21]=2[CH:40]=[O:41])=[CH:3]1.[BH4-].[Na+]>CO>[OH:41][CH2:40][C:21]1[C:22]([N:26]2[C:38](=[O:39])[C:37]3[S:36][C:35]4[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=4[C:29]=3[CH:28]=[N:27]2)=[N:23][CH:24]=[CH:25][C:20]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[S:11][C:12]3[CH2:13][N:14]([CH3:19])[CH2:15][CH2:16][C:17]=3[N:18]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866843984-[1-Methyl-5-({5-methyl-4H,6H,7H-[1,3]thiazolo[5,4-c]pyridin-2-yl}amino)-6-oxopyridin-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 866843993-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-oneYield 45.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of 216b (100 mg, 0.15 mmol) in methanol (6 mL) was added NaBH4 (18 mg, 0.45 mmol). The reaction mixture was stirred at 30° C. for 1 h and quenched with brine (10 mL). It was then evaporated under reduced pressure. The residue was extracted with dichloromethane (2×20 mL) and the combined organic layer was concentrated under reduced pressure. The resulting residue was purified by reverse-phase prep-HPLC to afford 216 as a white solid (40 mg, 40%). MS-ESI: [M+H]+ 588.3. 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J=5.0 Hz, 1H), 8.43 (d, J=2.0 Hz, 1H), 8.31 (s, 1H), 8.29 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.55 (d, J=5.0 Hz, 1H), 4.43-4.39 (m, 3H), 3.73 (s, 3H), 3.57-3.55 (m, 2H), 3.00-2.98 (m, 2H), 2.88-2.86 (m, 2H), 2.82-2.80 (m, 4H), 2.50 (s, 3H), 2.03-1.95 (m, 4H).

Workup

  1. customquenched with brine (10 mL)
  2. customIt was then evaporated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (2×20 mL)
  4. concentrationthe combined organic layer was concentrated under reduced pressure
  5. customThe resulting residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-9854f550f00e40538b9b8581bb58af30
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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