Triethylamine → N-[(3-bromo-4-fluorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}propanediamide

HRID 657294Notes

Reaction equation

HRID 657294 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].[Br:29][C:30]1[CH:31]=[C:32]([CH2:37][NH2:38])[CH:33]=[CH:34][C:35]=1[F:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>ClCCl>[Br:29][C:30]1[CH:31]=[C:32]([CH2:37][NH:38][C:23](=[O:24])[CH2:22][C:21]([NH:20][CH2:19][C:10]2[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]3[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]3=[N:8][C:9]=2[CH2:27][CH3:28])=[O:26])[CH:33]=[CH:34][C:35]=1[F:36]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724902(3-Bromo-4-fluorophenyl)methanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 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 57819933N-[(3-bromo-4-fluorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}propanediamideYield 106.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 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 (0.600 g, 1.541 mmol), 1-(3-bromo-4-fluorophenyl)methanamine (0.432 g, 1.796 mmol), HATU (0.760 g, 1.999 mmol) and triethylamine (0.600 mL, 4.30 mmol) in dichloromethane (35 mL) was stirred overnight at room temperature. The solution was diluted with DCM, washed with saturated NaHCO3, water followed by saturated NaCl, and dried over Na2SO4. The organic layer was evaporated to a pale amber residue. This was purified on 80 g. Combi-Flash column with DCM [0-8% MeOH] to give N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}propanediamide (942.9 mg, 106%, containing 12% impurities). LC-MS m/z 575.3 (M+H)+, 0.84 min (ret time).

Workup

  1. washwashed with saturated NaHCO3, water
  2. dry with materialdried over Na2SO4
  3. customThe organic layer was evaporated to a pale amber residue
  4. customThis was purified on 80 g

Sources & evidence

ORD record
ord-05c6b0110b7a414aa746481832d04b8f
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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