Triethylamine → 3-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-2,2-dimethyl-3-oxopropanoic acid

HRID 657379

Reaction equation

HRID 657379 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[C:9]([CH2:10][CH3:11])=[N:8][C:7]2[N:12]([CH2:15][CH3:16])[N:13]=[CH:14][C:6]=2[C:5]=1[NH:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.[CH3:24][C:25]([CH3:32])([C:29](O)=[O:30])[C:26]([OH:28])=[O:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[CH2:15]([N:12]1[C:7]2=[N:8][C:9]([CH2:10][CH3:11])=[C:4]([CH2:3][NH:2][C:29](=[O:30])[C:25]([CH3:32])([CH3:24])[C:26]([OH:28])=[O:27])[C:5]([NH:17][CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[C:6]2[CH:14]=[N:13]1)[CH3:16]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11686Dimethylmalonic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670055525-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride

Product 1

HCID 578198733-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-2,2-dimethyl-3-oxopropanoic acidYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride (400 mg, 1.18 mmol), dimethylpropanedioic acid (156 mg, 1.18 mmol), HBTU (535 mg, 1.41 mmol) and Et3N (0.82 mL, 5.89 mmol) in DCM (8 mL) was stirred at room temperature overnight. It was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with water followed by a brine wash. The organic layers were dried over sodium sulfate, filtered, concentrated and purified with CombiFlash eluting with 10% methanol in DCM. The product fractions were combined and concentrated to give 3-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-2,2-dimethyl-3-oxopropanoic acid as a solid (165 mg, 34%). LC-MS m/z 418 (M+H)+.

Workup

  1. customIt was quenched with saturated NaHCO3
  2. extractionextracted with DCM twice
  3. washThe combined organic layers were washed with water
  4. washwash
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified with CombiFlash
  9. washeluting with 10% methanol in DCM
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6df4e28bd98c4b63ab18a419f61e95bc
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Linked notes

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