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

HRID 662005Notes

Reaction equation

HRID 662005 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:28]=[C:27]([C:29](O)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[O:22])[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:34][C:35]1[CH:36]=[C:37]([CH2:41][NH2:42])[CH:38]=[CH:39][CH:40]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[Br:34][C:35]1[CH:36]=[C:37]([CH2:41][NH:42][C:29]([C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([C:21]([NH:20][CH2:19][C:10]3[C:11]([NH:12][CH:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[C:6]4[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]4=[N:8][C:9]=3[CH2:32][CH3:33])=[O:22])[N:28]=2)=[O:30])[CH:38]=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 457587Benzenemethanamine, 3-bromo-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578193746-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

Product 1

HCID 57819389N-[(3-bromophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamideYield 76.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid (600 mg, 1.326 mmol), 1-(3-bromophenyl)methanamine (247 mg, 1.326 mmol), HBTU (o-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate) (603 mg, 1.591 mmol) and Et3N (0.924 mL, 6.63 mmol) in DCM was stirred at room temperature over the weekend. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with brine and then concentrated under vacuum to give a crude residue. It was then purified with flash chromatography eluting with 0 to 100% ethyl acetate in hexane (product came out at 100% ethyl acetate in hexane). The product fractions were combined to give N-[(3-bromophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (632 mg, 49.9%). LC-MS m/z 620 (M+H)+, 0.89 min (ret time).

Workup

  1. customThe reaction was quenched with saturated NaHCO3
  2. extractionextracted with DCM twice
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated under vacuum
  5. customto give a crude residue
  6. customIt was then purified with flash chromatography
  7. washeluting with 0 to 100% ethyl acetate in hexane (product

Sources & evidence

ORD record
ord-aa7e2440a1c641c2a49b3c8d517ca591
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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