4-Cyanopiperidine → N-({3'-[(4-Cyano-1-piperidinyl)methyl]-6-fluoro-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 564643Notes

Reaction equation

HRID 564643 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[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:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=O)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[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].[NH:50]1[CH2:55][CH2:54][CH:53]([C:56]#[N:57])[CH2:52][CH2:51]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:56]([CH:53]1[CH2:54][CH2:55][N:50]([CH2:46][C:42]2[CH:41]=[C:40]([C:35]3[C:36]([F:39])=[CH:37][CH:38]=[C:33]([CH2:32][NH:31][C:29]([C:25]4[CH:26]=[CH:27][CH:28]=[C:23]([C:21]([NH:20][CH2:19][C:10]5[C:11]([NH:12][CH:13]6[CH2:14][CH2:15][O:16][CH2:17][CH2:18]6)=[C:6]6[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]6=[N:8][C:9]=5[CH2:48][CH3:49])=[O:22])[CH:24]=4)=[O:30])[CH:34]=3)[CH:45]=[CH:44][CH:43]=2)[CH2:51][CH2:52]1)#[N:57]

Participants

5

Reactant 3

HCID 1382234-CyanopiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 57813252N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-fluoro-3'-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide

Product 1

HCID 57813480N-({3'-[(4-Cyano-1-piperidinyl)methyl]-6-fluoro-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 28.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (82 mg, 0.129 mmol) in DCM (2.58 mL) was added 4-piperidinecarbonitrile (14.21 mg, 0.129 mmol), NaBH(OAc)3 (41.0 mg, 0.193 mmol). This mixture was stirred at room temperature for 19 h. The reaction mixture was washed with H2O (1 mL), concentrated, purified using a Gilson HPLC (with 0.1% TFA), and basified with an amine cartridge to afford 0.0274 g (28%) of the title compound. LC-MS m/z 757 (M+H)+; 1H NMR (400 MHz, MeOD) δ ppm 1.41 (t, J=7.53 Hz, 3 H) 1.49 (t, J=7.15 Hz, 3 H) 1.82-1.93 (m, J=13.05 Hz, 2 H) 1.96-2.38 (m, 6 H) 2.92-3.20 (m, 4 H) 3.22-3.29 (m, 1 H) 3.49-3.73 (m, 4 H) 4.00-4.09 (m, 2 H) 4.31-4.52 (m, 5 H) 4.62 (s, 2 H) 4.72 (s, 2 H) 7.20 (dd, J=10.54, 8.53 Hz, 1 H) 7.39-7.46 (m, 1 H) 7.50-7.65 (m, 4 H) 7.67-7.77 (m, 2 H) 8.05 (d, J=8.03 Hz, 2 H) 8.30 (s, 1 H) 8.39 (t, J=1.51 Hz, 1 H).

Workup

  1. washThe reaction mixture was washed with H2O (1 mL)
  2. concentrationconcentrated
  3. custompurified

Sources & evidence

ORD record
ord-c98bb4a472a04f89bde161cb350badd5
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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