Methanol → HCID 71143582, compound

HRID 627795Notes

Reaction equation

HRID 627795 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[CH2:30][C:29]5[C:28]([C:31]#[N:32])=[CH:27][CH:26]=[CH:25][C:24]=5[C:23]4=[O:33])=[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].CO.[BH4-].[Na+]>C(Cl)Cl>[NH2:32][CH2:31][C:28]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:29]=1[CH2:30][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)[C:23]2=[O:33]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 71143635HCID 71143635, compound

Product 1

HCID 71143582HCID 71143582, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]-1-oxo-isoindoline-4-carbonitrile (80 mg, 0.1143 mmol) dissolved in DCM (10 mL) and MeOH (5 mL) under N2. CoCl2 (29.68 mg, 0.2286 mmol) added and the reaction mixture cooled in an ice bath. NaBH4 (43 mg, 1.143 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 phase 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, s), 3.50 (1H, sep), 4.03 (2H, s), 5.59 (2H, s), 7.56 (1H, t), 7.71 (2H, m), 8.01 (2H, d), 8.51 (1H, s), 8.54 (2H, d), 9.12 (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 phase 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-6ffe58c6b43d413eb2564ee769933526
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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