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

HRID 657307Notes

Reaction equation

HRID 657307 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:28][CH3:29])=[C:10]([CH2:19][NH:20][C:21](=[O:27])[CH2:22][CH2:23][C:24](O)=[O:25])[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:30][C:31]1[CH:32]=[C:33]([CH2:38][NH2:39])[CH:34]=[CH:35][C:36]=1[CH3:37].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:30][C:31]1[CH:32]=[C:33]([CH2:38][NH:39][C:24](=[O:25])[CH2:23][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[CH2:28][CH3:29])=[O:27])[CH:34]=[CH:35][C:36]=1[CH3:37]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53414434(3-Bromo-4-methylphenyl)methanamineHCID 578198724-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-4-oxobutanoic acid

Product 1

HCID 57819894N-[(3-bromo-4-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-4-oxobutanoic acid (1.110 g, 2.75 mmol), 1-(3-bromo-4-methylphenyl)methanamine (0.600 g, 3.00 mmol), HATU (1.331 g, 3.5 mmol) and triethylamine (0.976 ml, 7.0 mmol) in dichloromethane (35 mL) was stirred at room temperature under N2. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and washed with saturated NaHCO3, followed by saturated NaCl. The organic layer was dried over Na2SO4, and then evaporated to dryness which gave, initially, a glassy gum, but then appeared to very slowly crystallize. The residue was taken up in a small amount of MeOH and sonicated whereupon a crystalline white solid formed and was collected and dried to give N-[(3-bromo-4-methylphenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (1.16 g, 72%). LC-MS m/z 585.4 (M+H)+, 0.87 min (ret time).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. washwashed with saturated NaHCO3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customevaporated to dryness which
  5. customgave
  6. customto very slowly crystallize
  7. customsonicated whereupon a crystalline white solid
  8. customformed
  9. customwas collected
  10. customdried

Sources & evidence

ORD record
ord-9b59b77faaa04de9bb8d3f2b0d1793bb
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…