N,N-Dimethylglycine → 1-[3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-2-(dimethylamino) 1-ethanone acetate

HRID 2056095Notes

Reaction equation

HRID 2056095 reaction equation
[C:1]([OH:4])(=[O:3])[CH3:2].[NH2:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]2[N:12]([CH:33]3[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]3)[N:13]=[C:14]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[O:23][C:24]5[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:25]=5[N:26]=4)=[CH:17][CH:16]=3)[C:7]=12.[CH3:39][N:40]([CH3:45])[CH2:41][C:42](O)=[O:43].Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2N=CC=CC=2N=N1>ClCCl>[C:1]([OH:4])(=[O:3])[CH3:2].[NH2:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]2[N:12]([CH:33]3[CH2:38][CH2:37][CH2:36][N:35]([C:42](=[O:43])[CH2:41][N:40]([CH3:45])[CH3:39])[CH2:34]3)[N:13]=[C:14]([C:15]3[CH:16]=[CH:17][C:18]([NH:21][C:22]4[O:23][C:24]5[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:25]=5[N:26]=4)=[CH:19][CH:20]=3)[C:7]=12

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22347309N2-{4-[4-amino-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl}-5,7-dimethyl-1,3-benzoxazol-2-amine acetate

Product 1

HCID 223466821-[3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-2-(dimethylamino) 1-ethanone acetateYield 38.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N2-{4-[4-amino-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl}-5,7-dimethyl-1,3-benzoxazol-2-amine acetate (0.04 g, 0.000078 mol), dimethylglycine (0.01 g, 0.000097 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.019 g, 0.000097 mol), N,N-diisopropylethylamine (0.033 g, 0.00026 mol) and 1-hydroxy-7-azabenzotriazole (0.011 g, 0.000078 mol) in anhydrous dichloromethane (5 mL) was stirred for 18 hours at room temperature. The solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane, and the combined organic solvent was washed with brine. The solvent was removed under reduced pressure, and the residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min) to yield 1-[3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidino]-2-(dimethylamino)-1-ethanone acetate (0.015 g, 0.00003 mol). 1H NMR (DMSO-d6, 400 MHz) δ 10.85 (s, 1H), 8.27 (d, 1H), 7.94 (d, 2H), 7.67 (d, 2H), 7.11 (s, 1H), 6.51 (s, 1H), 4.81-1.91 (br, 11H), 2.40 (s, 3H), 2.34 (s, 3H), 2.26 (s, 3H), 2.22 (s, 3H), 1.91 (s, 3H). RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-85% acetonitrile—0.1M ammonium acetate over 10 min, 1 mL/min) Rt 9.7 min.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between water and dichloromethane
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washthe combined organic solvent was washed with brine
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min)

Sources & evidence

ORD record
ord-3cf7528a9c0948eaab08c1eb0d6d35d6
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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