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

HRID 657303Notes

Reaction equation

HRID 657303 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]([OH:26])=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].[Br:30][C:31]1[CH:32]=[C:33]([CH2:38][NH2:39])[CH:34]=[CH:35][C:36]=1[Cl: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:26])[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[Cl: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 578133923-Bromo-4-chlorobenzylamineHCID 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 57819887N-[(3-bromo-4-chlorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamideYield 66.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL round-bottomed flask was added 4-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-4-oxobutanoic acid (1.0 g, 2.478 mmol), 1-(3-bromo-4-chlorophenyl)methanamine (0.595 g, 2.7 mmol), HATU (1.065 g, 2.8 mmol) and triethylamine (0.641 ml, 4.6 mmol) in dichloromethane (35 mL) to give a yellow suspension. The mixture was stirred overnight at room temperature. The reaction was quenched with saturated NaHCO3 and diluted with DCM. The organic layer were separated, then washed with water followed by saturated NaCl. The organic layer was dried over Na2SO4 and evaporated to a small volume, about 15 mL, from which a crystalline solid appeared which was collected, washed very sparingly with DCM and dried to give N-[(3-bromo-4-chlorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (1 g, 66.6%) as a solid. LC-MS m/z 605.5 (M+H)+, 0.75 min (ret time).

Workup

  1. customto give a yellow suspension
  2. customThe reaction was quenched with saturated NaHCO3
  3. additiondiluted with DCM
  4. customThe organic layer were separated
  5. washwashed with water
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customevaporated to a small volume, about 15 mL, from which a crystalline solid
  8. customwas collected
  9. washwashed very sparingly with DCM
  10. customdried

Sources & evidence

ORD record
ord-6dd6e21ba9ac48c09e9a8e9c2c33da93
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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