Acetic Acid → HCID 57813460, compound

HRID 564617Notes

Reaction equation

HRID 564617 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](C=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].[C@H:51]12[CH2:57][C@H:54]([NH:55][CH2:56]1)[CH2:53][N:52]2[C:58](OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>C(Cl)Cl>[C@H:51]12[CH2:57][C@H:54]([NH:55][CH2:56]1)[CH2:53][N:52]2[CH2:58][C:45]1[CH:46]=[C:41]([C:35]2[CH:36]=[CH:37][C:38]([O:39][CH3:40])=[C:33]([CH2:32][NH:31][C:29]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([C:21]([NH:20][CH2:19][C:10]4[C:11]([NH:12][CH:13]5[CH2:18][CH2:17][O:16][CH2:15][CH2:14]5)=[C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]5=[N:8][C:9]=4[CH2:49][CH3:50])=[O:22])[CH:24]=3)=[O:30])[CH:34]=2)[CH:42]=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 57813366HCID 57813366, compound

Product 1

HCID 57813460HCID 57813460, 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, 1,1-dimethylethyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (23 mg, 0.00012 mol) and sodium triacetoxyborohydride (34 mg., 0.00016 mol) and AcOH (6 uL) 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. The residue was taken up in DCM (10 mL) containing 25% TFA and allowed to stand at room temperature for 3 h. LC-MS showed the reaction to be complete. Solvent was stripped off. Purification was carried out on Gilson 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; 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 peach colored solid [40.9 mg (68%)]. LC-MS m/z 757.5 (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. additioncontaining 25% TFA
  8. customthe reaction
  9. customPurification
  10. additionFractions containing the clean desired product
  11. additiondiluted with EtOAc
  12. washwashed with sat. aq. NaHCO3
  13. extractionaq. phase was back-extracted with EtOAc
  14. washCombined organic extracts were washed with sat. aq. NaCl
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-56c64b52476a4cc19291e5a1ae31d18c
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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