Hydrochloric Acid → HCID 135938506, compound

HRID 1798744Notes

Reaction equation

HRID 1798744 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:16][C:17]([N:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([O:32][CH3:33])[CH:26]=4)[CH2:21][CH2:20]3)=[O:18])[N:9]=[C:10]([C:11]3[NH:12][CH:13]=[CH:14][N:15]=3)[C:3]=12.O.[ClH:35]>CC(C)=O>[ClH:31].[ClH:35].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:16][C:17]([N:19]3[CH2:20][CH2:21][N:22]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([O:32][CH3:33])[CH:26]=4)[CH2:23][CH2:24]3)=[O:18])[N:9]=[C:10]([C:11]3[NH:15][CH:14]=[CH:13][N:12]=3)[C:3]=12

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 135882281HCID 135882281, compound

Product 1

HCID 135938506HCID 135938506, compoundYield 170.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a mixture of 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]ethanone (50 g, 0.1068 mol), H2O (250 mL), and acetone (750 mL) at 60° C. was added concentrated HCl (22.3 mL, 0.267 mol, 2.50 equiv) dropwise to give a brown solution. After 90 min, a thick tan suspension formed. The suspension was diluted to a final concentration of 0.03 M by dropwise addition of acetone (2.1 L) while maintaining the internal temperature between 58° C. to 62° C. The resulting mixture was stirred at 60° C. for another 90 min, cooled to room temperature, and filtered. The solid was washed with acetone (60 mL×2) and dried in vacuo to afford 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]ethanone dihydrochloride salt (49.2 g, 80% yield, >99% pure by LC-MS) as fine tan prisms. 1H NMR (400 MHz, d6-DMSO) δ 13.45 (s, 1H), 11.92 (s, 1H), 9.43 (s, 1H), 8.50 (s, 1H), 7.33 (s, 2H), 7.22 (d, 1H, J=8.8 Hz), 6.72 (d, 1H, J=2.4 Hz), 6.55 (dd, 1H, J=2.4, 8.8 Hz), 5.54 (s, 2H), 3.84 (s, 3H), 3.76 (t, 2H, J=4.8 Hz), 3.61 (t, 2H, J=4.8 Hz), 3.31 (t, 2H, J=4.8 Hz), 3.20 (t, 2H, J=4.8 Hz). MS (ES) m/z 468.1(M+H+). Anal. Calcd for C21H22N9O2Cl-2HCl-1.75H2O: C, 44.07; H, 4.84; N, 22.02; Cl, 18.58. Found: C, 43.89; H, 4.48; N, 22.0; Cl, 18.26. KF (H2O) Calcd for C21H22N9O2Cl-2HCl-1.75H2O: 5.51%. Found: 5.14%.

Workup

  1. customto give a brown solution
  2. customa thick tan suspension formed
  3. temperaturewhile maintaining the internal temperature between 58° C. to 62° C
  4. temperaturecooled to room temperature
  5. filtrationfiltered
  6. washThe solid was washed with acetone (60 mL×2)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-c81943b595e144dcb05dba30e8ea5d52
Source dataset
uspto-grants-2013_01
Patent number
US08343975B2

Reaction notes

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