Sodium borohydride → HCID 71143632, compound

HRID 627796Notes

Reaction equation

HRID 627796 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:28]([C:32]#[N:33])=[CH:27][CH:26]=[CH:25][C:24]=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:28]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:29]=1[C:30](=[O:31])[N:22]([C:21]1[C:15]3[C:16](=[N:17][CH:18]=[C:13]([C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:8][CH:9]=4)[N:14]=3)[NH:19][CH:20]=1)[CH2:23]2

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 71143564HCID 71143564, compound

Product 1

HCID 71143632HCID 71143632, 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-4-carbonitrile (150 mg, 0.2143 mmol) dissolved in a mixture of DCM (10 mL) and MeOH (5 mL) under N2. CoCl2 (55.65 mg, 0.4286 mmol) added then the reaction mixture cooled in an ice bath. NaBH4 (81 mg, 2.143 mmol) added in one portion. Ice bath removed and mixture stirred for 3 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 black 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), 4.17 (2H, s), 5.50 (2H, s), 7.51-7.53 (1H, m), 7.62-7.65 (3H, m), 8.00 (2H, d), 8.51-8.54 (3H, m), 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 black foam

Sources & evidence

ORD record
ord-75611d7ac13842d1947eef471e330661
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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