Sodium borohydride → HCID 71143644, compound

HRID 627797Notes

Reaction equation

HRID 627797 reaction equation
[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[C:21]([N:22]4[C:30](=[O:31])[C:29]5[C:24](=[CH:25][CH:26]=[C:27]([C:32]#[N:33])[CH:28]=5)[CH2:23]4)=[CH:20][N:19](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:16]3=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].[BH4-].[Na+]>C(Cl)Cl.CO>[NH2:33][CH2:32][C:27]1[CH:28]=[C:29]2[C:24]([CH2:23][N:22]([C:21]3[C:15]4[C:16](=[N:17][CH:18]=[C:13]([C:10]5[CH:11]=[CH:12][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:8][CH:9]=5)[N:14]=4)[NH:19][CH:20]=3)[C:30]2=[O:31])=[CH:25][CH:26]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 71245690HCID 71245690, compound

Product 1

HCID 71143644HCID 71143644, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]-3-oxo-isoindoline-5-carbonitrile (130 mg, 0.1858 mmol) dissolved in a mixture of DCM (10 mL) and MeOH (5 mL) under N2. CoCl2 (48.25 mg, 0.3716 mmol) added then the reaction mixture cooled in an ice bath. NaBH4 (70 mg, 1.858 mmol) added in one portion. Ice bath removed and mixture stirred for 2 h then cooled in an ice bath and water (˜5 mL) added. Mixture diluted with DCM (˜20 mL) and stirred vigorously for 20 mins. Layers separated and aqueous extracted with DCM. Aqueous phase basified by addition of sat NaHCO3 solution and extracted with DCM (×2). Combined organics dried and concentrated to a brown foam. This material deprotected using Method E Step 2 to give the title compound after purification by hplc; 1H NMR (400 MHz, DMSO) δ 1.21 (6H, d), 3.50 (1H, sep), 3.88 (2H, s), 5.49 (2H, s), 7.65 (1H, d), 7.71 (1H, d), 7.84 (1H, s), 8.00 (2H, d), 8.51-8.53 (3H, m), 9.09 (1H, s) ppm; MS (ES+) 462.0.

Workup

  1. temperaturethe reaction mixture cooled in an ice bath
  2. customIce bath removed
  3. temperaturethen cooled in an ice bath
  4. additionwater (˜5 mL) added
  5. additionMixture diluted with DCM (˜20 mL)
  6. stirringstirred vigorously for 20 mins
  7. customLayers separated
  8. extractionaqueous extracted with DCM
  9. additionAqueous phase basified by addition of sat NaHCO3 solution
  10. extractionextracted with DCM (×2)
  11. customCombined organics dried
  12. concentrationconcentrated to a brown foam

Sources & evidence

ORD record
ord-bb88b58e8d6d4deba457cfa3a57fb0ea
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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