Triethylamine → HCID 178488221, compound

HRID 897537

Reaction equation

HRID 897537 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].C(N(CC)CC)C.[C:40](Cl)(=[O:49])[CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>ClCCl>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:40](=[O:49])[CH2:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 64801Benzenepropanoyl chloride2×HCID 178488197HCID 178488197, compound

Product 1

HCID 178488221HCID 178488221, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of cis-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (75 mg, 0.17 mmol) and triethylamine (34 mg, 0.34 mmol) in dichloromethane (2.5 ml) was added hydrocinnamoyl chloride (34 mg, 0.20 mmol) in dichloromethane (0.5 ml) dropwise. The solution was stirred at room temperature for 48 hr and a further equivalent of hydrocinnamoyl chloride was then added. The reaction mixture was stirred for a further 24 hr. The resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml) and passed through an Empore extraction cartridge. Evaporation of the solvent gave an oily solid which was purified by silica gel chromatography using 10-20% MeOH/dichloromethane to give cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-3-phenylpropanamide (12 mg, 13%). 1H NMR (CDCl3): δH 8.55 (1H, d), 8.36 (1H, s), 7.75 (1H, s), 7.25 (7H, m), 5.51 (2H, bs), 4.91 (1H, m), 3.92 (3H, s), 3.09 (2H, m), 2.76 (2H, m), 2.34-2.59 (9H, m), 2.29 (3H, s), 2.16 (2H, m), 1.85 (4H, m), 1.66 (2H, m). LCMS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 3.5 mL/min.) Rt=1.92 mins, MH+=569.6.

Workup

  1. stirringThe reaction mixture was stirred for a further 24 hr
  2. customThe resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml)
  3. extractionpassed through an Empore extraction cartridge
  4. customEvaporation of the solvent
  5. customgave an oily solid which
  6. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-45bc16756df546e8a8cce3877b54d934
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Linked notes

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