Pyridine → HCID 178488195, compound

HRID 432413

Reaction equation

HRID 432413 reaction equation
[C:1]1([C@H:7]([CH3:12])[CH2:8]C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13](Cl)(=[O:17])C(Cl)=O.N[C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:34]3[C:29](=[N:30][CH:31]=[N:32][C:33]=3[NH2:35])[N:28]([C@H:36]3[CH2:41][CH2:40][C@H:39]([N:42]4[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]4)[CH2:38][CH2:37]3)[N:27]=2)=[CH:22][C:21]=1[O:49][CH3:50].C(OCC)(=O)C.[N:57]1C=CC=CC=1>ClCCl.CN(C=O)C>[C:1]1([C@@H:7]([CH3:12])[CH2:8][NH:57][C:13](=[O:17])[C:20]2[CH:25]=[CH:24][C:23]([C:26]3[C:34]4[C:29](=[N:30][CH:31]=[N:32][C:33]=4[NH2:35])[N:28]([C@H:36]4[CH2:41][CH2:40][C@H:39]([N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]5)[CH2:38][CH2:37]4)[N:27]=3)=[CH:22][C:21]=2[O:49][CH3:50])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 852992(3R)-3-phenylbutanoic acidHCID 178488198HCID 178488198, compound

Product 1

HCID 178488195HCID 178488195, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To (3R)-3-phenylbutanoic acid (376 mg, 2.29 mmol) in dichloromethane (7 mL) was added oxalyl chloride (2 mL, 22.9 mmol) and DMF (1 drop). The reaction mixture was stirred overnight. Solvent was evaporated and the residue was dissolved in dichloromethane (3 mL). The dichloromethane solution was added to a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (448 mg, 1.026 mmol) in pyridine (6 mL) at 0° C. After 2 hours, the reaction mixture was poured to ethyl acetate (60 ml) and the solid as collected by filtration. Water was then added to the solid and the pH of the solution was adjusted to 10 with sodium hydroxide (1.0N). The aqueous was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-N1-[(2R)-2-phenylpropyl]-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (383 mg, 64%). 1H NMR (CDCl3) δ 1.40 (d, J=6.96, 3H), 1.57 (m, 2H), 2.08-2.21 (m, 6H), 2.30 (s, 3H), 2.50 (m, 5H), 2.63-2.74 (m, 6H), 3.40 (m, 1H), 3.88 (s, 3H), 4.74 (m, 1H), 5.69 (bs, 2H), 7.16-7.34 (m, 7H), 7.66 (s, 1H), 8.34 (s, 1H), 8.49 (d, J=8.21, 1H).

Workup

  1. customSolvent was evaporated
  2. dissolutionthe residue was dissolved in dichloromethane (3 mL)
  3. waitAfter 2 hours
  4. filtrationthe solid as collected by filtration
  5. additionWater was then added to the solid
  6. extractionThe aqueous was extracted with dichloromethane
  7. washThe combined organic layer was washed with water
  8. dry with materialbrine, dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-467258d7343346eda7b8f51d658c9429
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Linked notes

Loading…