Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}propanediamide

HRID 657406Notes

Reaction equation

HRID 657406 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:27][CH3:28])=[C:10]([CH2:19][NH:20][C:21](=[O:26])[CH2:22][C:23](O)=[O:24])[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].[NH2:29][CH2:30][C:31]1[CH:32]=[C:33]([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][CH:44]3[CH2:49][CH2:48][N:47](C(OC(C)(C)C)=O)[CH2:46][CH2:45]3)[CH:38]=2)[CH:34]=[CH:35][CH:36]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:27][CH3:28])=[C:10]([CH2:19][NH:20][C:21](=[O:26])[CH2:22][C:23]([NH:29][CH2:30][C:31]3[CH:32]=[C:33]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][CH:44]5[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]5)[CH:38]=4)[CH:34]=[CH:35][CH:36]=3)=[O:24])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57813360tert-Butyl 4-{[3'-(aminomethyl)biphenyl-3-yl]methyl}piperidine-1-carboxylateHCID 578198663-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-3-oxopropanoic acid

Product 1

HCID 57819902N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}propanediamideYield 25.24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of 3-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-3-oxopropanoic acid (0.0779 g, 0.200 mmol) in DCM (1 mL) was added 1,1-dimethylethyl 4-{[3′-(aminomethyl)-3-biphenylyl]methyl}-1-piperidinecarboxylate (0.0837 g, 0.220 mmol), HBTU (0.0910 g, 0.240 mmol), TEA (0.0563 mL, 0.400 mmol) and was stirred at room temperature for 16 hours. The reaction mixture was concentrated on Glas-Col evaporator, purified by Gilson HPLC and concentrated with Biotachi evaporator. The crude product was dissolved in DCM (0.6 mL) and TFA (0.2 mL) was added. The resultant mixture was left at room temperature for 1 hour before being concentrated on Glas-Col evaporator, purified by Gilson HPLC (with 0.1% TFA) and basified with amine cartridge to afford the title compound 0.0329 g (25.24%). LC-MS m/z 652 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.38 (t, J=7.65 Hz, 3H) 1.49 (t, J=7.28 Hz, 5H) 1.72-1.85 (m, 2H) 1.87-2.02 (m, 5H) 2.69 (d, J=6.78 Hz, 2H) 2.94 (td, J=12.80, 2.26 Hz, 2H) 3.05 (q, J=7.53 Hz, 2H) 3.37 (d, J=12.55 Hz, 2H) 3.59 (td, J=11.48, 2.13 Hz, 2H) 3.92 (dt, J=1.80, 3.51 Hz, 2H) 4.19-4.30 (m, 1H) 4.42-4.50 (m, 4H) 4.52 (s, 2H) 7.19 (d, J=7.53 Hz, 1H) 7.27-7.32 (m, 1H) 7.37 (td, J=7.59, 3.14 Hz, 2H) 7.44-7.52 (m, 3H) 7.57 (s, 1H) 8.24 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated on Glas-Col evaporator
  2. custompurified by Gilson HPLC
  3. concentrationconcentrated with Biotachi evaporator
  4. dissolutionThe crude product was dissolved in DCM (0.6 mL)
  5. additionTFA (0.2 mL) was added
  6. waitThe resultant mixture was left at room temperature for 1 hour
  7. concentrationbefore being concentrated on Glas-Col evaporator
  8. custompurified by Gilson HPLC (with 0.1% TFA)

Sources & evidence

ORD record
ord-1eacf881af10472db33a70954bff42a7
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…