Acetic Acid → HCID 57813407, compound

HRID 564621Notes

Reaction equation

HRID 564621 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH:47]=O)[CH:42]=5)[CH:36]=[CH:37][C:38]=4[O:39][CH3:40])=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH3:51][N:52]1[CH2:58][CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:55]6[CH2:56][CH2:57][CH2:58][N:52]([CH3:51])[CH2:53][CH2:54]6)[CH:42]=5)[CH:36]=[CH:37][C:38]=4[O:39][CH3:40])=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2283491-MethylhomopiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 57813366HCID 57813366, compound

Product 1

HCID 57813407HCID 57813407, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[3′-formyl-4-(methyloxy)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide (54 mg, 0.00008 mol) in DCM, 1-methylhexahydro-1H-1,4-diazepine (13.7 mg, 15.2 μL, 0.00012 mol) and sodium triacetoxyborohydride (34 mg., 0.00016 mol) and AcOH (6 μL) were agitated overnight on a shaker. LC-MS was used to monitor the reaction. The reaction was quenched with sat. aq. NaHCO3, then extracted with DCM (2×). Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. Purification was carried out on Gilson HPLC instrument with acetonitrile-water (0.1% TFA) gradient; C18-RP column. Fractions containing the clean desired product were combined; diluted with EtOAc; washed with sat. aq. NaHCO3; and the aq. phase was back-extracted with EtOAc. Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. It was taken up in a small amount of DCM and transferred to a vial and pumped down to afford the title compound as a chalky white solid. Further purification was carried out on an Agilent HPLC with RP-CH3CN:H2O-conc. aq. NH3 gradient [4.5 mg (7.25%)]. LC-MS m/z 773.5 (M+H)+.

Workup

  1. customthe reaction
  2. customThe reaction was quenched with sat. aq. NaHCO3
  3. extractionextracted with DCM (2×)
  4. washCombined organic extracts were washed with sat. aq. NaCl
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to a residue
  7. customPurification
  8. additionFractions containing the clean desired product
  9. additiondiluted with EtOAc
  10. washwashed with sat. aq. NaHCO3
  11. extractionand the aq. phase was back-extracted with EtOAc
  12. washCombined organic extracts were washed with sat. aq. NaCl
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-4015b4ddc12b42f5baaf1547fbbf9c69
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

Loading…