Diisopropylethylamine → HCID 22347040, compound

HRID 432514Notes

Reaction equation

HRID 432514 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:29][CH2:28][N:27]([CH2:30][C:31](O)=[O:32])[CH2:26][CH2:25]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.S(O)(O)(=O)=O.[NH2:39][C:40]1[NH:41][CH:42]=[CH:43][N:44]=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2N=CC=CC=2N=N1>ClCCl>[NH:41]1[CH:42]=[CH:43][N:44]=[C:40]1[NH:39][C:31](=[O:32])[CH2:30][N:27]1[CH2:26][CH2:25][CH:24]([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]3[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][CH:12]=3)=[N:9]2)[CH2:29][CH2:28]1

Participants

7

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 135136Bis(2-amino-1H-imidazole) sulphate2×HCID 181649HOAt2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 22347376HCID 22347376, compound

Product 1

HCID 22347040HCID 22347040, compoundYield 7.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidino}acetic acid (0.06 g, 0.00013 mol), 2-aminoimidazole sulfate (0.022 g, 0.000163 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.031 g, 0.000163 mol), N,N-diisopropylethylamine (0.047 g, 0.00036 mol) and 1-hydroxy-7-azabenzotriazole (0.018 g, 0.00013 mol) in anhydrous dichloromethane (8 mL) was stirred for 18 hours at room temperature. Additional 2-aminoimidazole sulfate (0.022 g, 0.000163 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.031 g, 0.000163 mol), N,N-diisopropylethylamine (0.047 g, 0.00036 mol) and 1-hydroxy-7-azabenzotriazole (0.018 g, 0.00013 mol), were added and the mixture was stirred for 18 hour at room temperature. The mixture was warmed to 50° C. for 6 hours, then stirred at room temperature for 2 days. 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 N1-(1H-2-imidazolyl)-2-{4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidino}acetamide (0.005 g, 0.00001 mol).

Workup

  1. stirringthe mixture was stirred for 18 hour at room temperature
  2. temperatureThe mixture was warmed to 50° C. for 6 hours
  3. stirringstirred at room temperature for 2 days
  4. customThe solvent was removed under reduced pressure
  5. 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-98e425c3cb6349918f709aafc43a6938
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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