Acetic Acid → N-({6-Chloro-3'-[(4-methylhexahydro-1H-1,4-diazepin-1-yl)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 564589Notes

Reaction equation

HRID 564589 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([NH:28][CH2:29][C:30]3[C:31]([NH:43][CH:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[C:32]4[CH:40]=[N:39][N:38]([CH2:41][CH3:42])[C:33]4=[N:34][C:35]=3[CH2:36][CH3:37])=[O:27])[CH:21]=2)=[O:19])=[CH:4][CH:3]=1.[CH3:50][N:51]1[CH2:57][CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:54]3[CH2:55][CH2:56][CH2:57][N:51]([CH3:50])[CH2:52][CH2:53]3)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([NH:28][CH2:29][C:30]3[C:31]([NH:43][CH:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[C:32]4[CH:40]=[N:39][N:38]([CH2:41][CH3:42])[C:33]4=[N:34][C:35]=3[CH2:36][CH3:37])=[O:27])[CH:21]=2)=[O:19])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2283491-MethylhomopiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 57813357HCID 57813357, compound

Product 1

HCID 57813345N-({6-Chloro-3'-[(4-methylhexahydro-1H-1,4-diazepin-1-yl)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

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

N-[(6-Chloro-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 (0.034 g, 0.05 mmol), 1-methylhexahydro-1H-1,4-diazepine (0.0069 g, 0.06 mmol), and acetic acid (0.0036 g, 0.06 mmol) were combined in 1,2-dichloroethane (2 mL). The reaction mixture was stirred for 30 min. Sodium triacetoxyborohydride (0.0148 g, 0.07 mmol) was added and the mixture stirred overnight at room temperature. Solvents were concentrated, and the residue taken up in EtOAc, washed with 1N NaOH, brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the crude product. The product was purified using a Gilson HPLC with a TFA system. The purified compound was taken up in EtOAc, washed 3× with 2.5 N NaOH, 1× with brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the title compound as a white solid. LC-MS m/z 777.1 (M+H)+, 1.39 min (ret time); mp 105-107° C. Analytical HPLC shows 95.3% purity, (ret time 10.044 min).

Workup

  1. stirringthe mixture stirred overnight at room temperature
  2. concentrationSolvents were concentrated
  3. washwashed with 1N NaOH, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe product was purified
  9. washwashed 3× with 2.5 N NaOH, 1× with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-12af7eb632cb4b739baae41c0bab9219
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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