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}pentanediamide

HRID 657420Notes

Reaction equation

HRID 657420 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:29][CH3:30])=[C:10]([CH2:19][NH:20][C:21](=[O:28])[CH2:22][CH2:23][CH2:24][C:25]([OH:27])=O)[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].[NH2:31][CH2:32][C:33]1[CH:34]=[C:35]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][CH:46]3[CH2:51][CH2:50][N:49](C(OC(C)(C)C)=O)[CH2:48][CH2:47]3)[CH:40]=2)[CH:36]=[CH:37][CH:38]=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]([CH2:29][CH3:30])=[C:10]([CH2:19][NH:20][C:21](=[O:28])[CH2:22][CH2:23][CH2:24][C:25]([NH:31][CH2:32][C:33]3[CH:34]=[C:35]([C:39]4[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][CH:46]5[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]5)[CH:40]=4)[CH:36]=[CH:37][CH:38]=3)=[O:27])[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 578198975-({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-5-oxopentanoic Acid

Product 1

HCID 44242619N-{[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}pentanediamideYield 35.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-5-oxopentanoic acid (0.0807 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), and TEA (0.0562 mL, 0.400 mmol), and was stirred at room temperature for 16 h. The reaction mixture was concentrated on a Glas-Col evaporator, purified using a 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 h before being concentrated on a Glas-Col evaporator, purified using a Gilson HPLC (acidic conditions: with 0.1% TFA) and basified with an amine cartridge to afford the title compound 0.048 g (35%). LC-MS m/z 680.

Workup

  1. concentrationThe reaction mixture was concentrated on a Glas-Col evaporator
  2. custompurified
  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 h
  7. concentrationbefore being concentrated on a Glas-Col evaporator
  8. custompurified

Sources & evidence

ORD record
ord-f5ef1342023d4f0e86607f50388b1f39
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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