Diisopropylethylamine → HCID 57964912, compound

HRID 1931747Notes

Reaction equation

HRID 1931747 reaction equation
FC(F)(F)C(O)=O.[CH3:8][S:9]([C:12]1[CH:33]=[CH:32][C:15]([O:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[N:24]=[CH:25][C:18]=23)=[CH:14][CH:13]=1)(=[O:11])=[O:10].C(N(CC)C(C)C)(C)C.[CH3:43][CH:44]([CH3:50])[CH2:45][CH2:46][C:47](Cl)=[O:48]>ClCCl>[CH3:8][S:9]([C:12]1[CH:13]=[CH:14][C:15]([O:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([CH:26]4[CH2:27][CH2:28][N:29]([C:47](=[O:48])[CH2:46][CH2:45][CH:44]([CH3:50])[CH3:43])[CH2:30][CH2:31]4)[N:24]=[CH:25][C:18]=23)=[CH:32][CH:33]=1)(=[O:11])=[O:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 170008Pentanoyl chloride, 4-methyl-HCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 57964912HCID 57964912, compoundYield 55.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 60 mg, 0.123 mmol) and N,N-diisopropylethylamine (0.11 mL, 0.615 mmol) in dichloromethane (1.0 mL) at room temperature was added 4-methylvaleroyl chloride (Pfaltz & Bauer, Inc., Waterbury, Conn., USA; 20 mg; 0.15 mmol). After 1 h, the mixture was washed with 1 N HCl followed by water. The organic layer was dried (sodium sulfate), filtered and concentrated in vacuo. The crude product was triturated with diethyl ether, filtered, washed with diethyl ether and allowed to air dry to provide 1-{4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-4-methyl-pentan-1-one (32 mg, 55%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 0.87 (d, 6H, J=6.6 Hz), 1.36-1.44 (m, 2H), 1.50-1.59 (m, 1H), 1.94-2.10 (m, 4H), 2.33-2.38 (m, 2H), 2.74-2.86 (m, 1H), 3.30 (water peak and SO2CH3), 3.98-4.08 (m, 1H), 4.46-4.57 (m, 1H), 5.00-5.14 (m, 1H), 7.62 (d, 2H, J=8.5 Hz), 8.04 (d, 2H, J=8.7 Hz), 8.38 (s, 1H), 8.55 (s, 1H). Mass spectrum MH+=472.

Workup

  1. washthe mixture was washed with 1 N HCl
  2. dry with materialThe organic layer was dried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was triturated with diethyl ether
  6. filtrationfiltered
  7. washwashed with diethyl ether
  8. customto air dry

Sources & evidence

ORD record
ord-ad149dd82f1d4c3baa996f80d26944f6
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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