Diisopropylethylamine → tert-butyl N-(3-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidino}-3-oxopropyl)-N-(2-hydroxyethyl)carbamate

HRID 432511Notes

Reaction equation

HRID 432511 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:34][C:35]([N:37]([CH2:43][CH2:44][OH:45])[CH2:38][CH2:39][C:40](O)=[O:41])=[O:36])([CH3:33])([CH3:32])[CH3:31].Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2N=CC=CC=2N=N1>ClCCl>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([CH:24]3[CH2:29][CH2:28][N:27]([C:40](=[O:41])[CH2:39][CH2:38][N:37]([CH2:43][CH2:44][OH:45])[C:35](=[O:36])[O:34][C:30]([CH3:31])([CH3:32])[CH3:33])[CH2:26][CH2:25]3)[N:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:13][CH:12]=3)[C:22]=12

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 223469613-{[(Tert-butoxy)carbonyl](2-hydroxyethyl)amino}propanoicacidHCID 223472623-(4-phenoxyphenyl)-1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 18761469tert-butyl N-(3-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidino}-3-oxopropyl)-N-(2-hydroxyethyl)carbamateYield 63.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(4-phenoxyphenyl)-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.05 g, 0.00013 mol), 3-[(tert-butoxycarbonyl)(2-hydroxyethyl)amino]propanoic acid (0.038 g, 0.000163 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.031 g, 0.000163 mol), N,N-diisopropylethylamine (0.031 g, 0.00024 mol) and 1-hydroxy-7-azabenzotriazole (0.018 g, 0.00013 mol) in anhydrous dichloromethane (5 mL) was stirred for 18 hours at room temperature. The solvent was removed under reduced pressure. 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 tert-butyl N-(3-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidino}-3-oxopropyl)-N-(2-hydroxyethyl)carbamate (0.050 g, 0.000083 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 10.4 min. MS: MH+ 602.

Workup

  1. customThe solvent was removed under reduced pressure
  2. 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-5a65d3efa99c4ed8a7885be0db8719f3
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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