Acetic Acid → N-({6-Cyano-3'-[(4-methyl-1-piperazinyl)methyl]-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

HRID 564614Notes

Reaction equation

HRID 564614 reaction equation
[C:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11](C=O)[CH:10]=2)=[CH:7][C:6]([CH2:17][NH:18][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([NH:29][CH2:30][C:31]3[C:32]([NH:44][CH:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[C:33]4[CH:41]=[N:40][N:39]([CH2:42][CH3:43])[C:34]4=[N:35][C:36]=3[CH2:37][CH3:38])=[O:28])[CH:22]=2)=[O:20])=[CH:5][CH:4]=1)#[N:2].[CH3:51][N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.[C:58](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>C(Cl)Cl>[C:1]([C:3]1[C:8]([C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:51][N:52]3[CH2:57][CH2:56][N:55]([CH3:58])[CH2:54][CH2:53]3)[CH:14]=2)=[CH:7][C:6]([CH2:17][NH:18][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([NH:29][CH2:30][C:31]3[C:32]([NH:44][CH:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[C:33]4[CH:41]=[N:40][N:39]([CH2:42][CH3:43])[C:34]4=[N:35][C:36]=3[CH2:37][CH3:38])=[O:28])[CH:22]=2)=[O:20])=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 57813346HCID 57813346, compound

Product 1

HCID 57813391N-({6-Cyano-3'-[(4-methyl-1-piperazinyl)methyl]-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamideYield 36.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(6-Cyano-3′-formyl-3-biphenylyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (108 mg, 0.000161 mol) in DCM (4 mL) and 1-methylpiperazine (23.4 mg, 0.00023 mol) were mixed with sodium triacetoxyborohydride (68.3 mg, 0.00032 mol) and AcOH (11.6 mg, 11 μL). The solution was stirred overnight at room temperature. LC-MS showed that the reaction was complete. The reaction was quenched with sat. aq. NaHCO3, then extracted with DCM (2×). The combined organic extracts were washed with sat. aq. NaCl, dried (Na2SO4) and concentrated to a glassy foam (98.9 mg). Purification was carried out on Gilson instrument with an 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 back-extracted with EtOAc. The combined organic layers 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 white solid [43.9 mg (36%)]. LC-MS m/z 769.7 (M+H)+.

Workup

  1. customThe reaction was quenched with sat. aq. NaHCO3
  2. extractionextracted with DCM (2×)
  3. washThe combined organic extracts were washed with sat. aq. NaCl
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to a glassy foam (98.9 mg)
  6. customPurification
  7. additionFractions containing the clean desired product
  8. additiondiluted with EtOAc
  9. washwashed with sat. aq. NaHCO3
  10. extractionand the aq. phase back-extracted with EtOAc
  11. washThe combined organic layers were washed with sat. aq. NaCl
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-49f4d8a2aecb482ba0da174c595ec1f3
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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