Sodium borohydride → 3-[3-(Hydroxymethyl)-4-[1-methyl-6-oxo-5-(pyrazin-2-ylamino)-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-one

HRID 1021888Notes

Reaction equation

HRID 1021888 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[N:14][CH:13]=[CH:12][N:11]=2)=[CH:5][C:4]([C:16]2[CH:21]=[CH:20][N:19]=[C:18]([N:22]3[C:34](=[O:35])[C:33]4[S:32][C:31]5[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=5[C:25]=4[CH:24]=[N:23]3)[C:17]=2[CH:36]=[O:37])=[CH:3]1.[BH4-].[Na+]>CO>[OH:37][CH2:36][C:17]1[C:18]([N:22]2[C:34](=[O:35])[C:33]3[S:32][C:31]4[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=4[C:25]=3[CH:24]=[N:23]2)=[N:19][CH:20]=[CH:21][C:16]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[N:14][CH:13]=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866843564-{1-Methyl-6-oxo-5-[(pyrazin-2-yl)amino]-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 866843573-[3-(Hydroxymethyl)-4-[1-methyl-6-oxo-5-(pyrazin-2-ylamino)-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-oneYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 194b (200 mg, 0.4 mmol) and NaBH4 (48 mg, 1.2 mmol) in methanol (20 mL) was stirred at 30° C. for 2 h. The mixture was quenched with water (5 mL) and concentrated under reduced pressure. The residue was extracted with ethyl acetate (3×10 mL). The combined with ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 194 (60 mg, 30%) as a white solid. MS-ESI: [M+H]+ 514.2. 1H NMR (500 MHz, CDCl3) δ 8.78 (d, J=2.0 Hz, 1H), 8.69 (d, J=5.0 Hz, 1H), 8.31 (s, 1H), 8.29 (s, 1H), 8.17 (s, 1H), 8.13 (s, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.83 (d, J=2.5 Hz, 1H), 7.56 (d, J=5 Hz, 1H), 4.44-4.37 (m, 3H), 3.76 (s, 3H), 3.01-2.99 (m, 2H), 2.88-2.86 (m, 2H), 2.01-1.96 (m, 4H).

Workup

  1. customThe mixture was quenched with water (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with ethyl acetate (3×10 mL)
  4. extractionextract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-10c316d8d4be4f1fbc342c310a07d43f
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

Loading…