Potassium Carbonate → 3-(2,5-Dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine

HRID 1842688Notes

Reaction equation

HRID 1842688 reaction equation
C([O-])([O-])=O.[K+].[K+].[OH-].[K+].C(O/[CH:14]=[CH:15]/[C:16]1[C:21]([Cl:22])=[CH:20][N:19]=[C:18]([Cl:23])[N:17]=1)CCC.[I-].[NH2:25][N+:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CS(C)=O.O>[Cl:23][C:18]1[N:17]=[C:16]([C:15]2[CH:14]=[N:25][N:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=23)[C:21]([Cl:22])=[CH:20][N:19]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 2733704Pyridinium, 1-amino-, iodide (1:1)HCID 46934604HCID 46934604, compound2×

Product 1

HCID 592911623-(2,5-Dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridineYield 20.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

K2CO3 (20.82 g, 150.65 mmol) and KOH (16.91 g, 301.31 mmol) were added in one portion to a mixture of (E)-4-(2-butoxyvinyl)-2,5-dichloropyrimidine (Intermediate 22, 74.46 g, 301.31 mmol) and 1-aminopyridinium iodide (66.9 g, 301.31 mmol) in DMSO (1.415 L) at r.t. The mixture was stirred at r.t. for 1.5 h and then at 90° C. for 4 h. After cooling, the mixture was diluted with water (5 L) and stirred for 0.5 h. The resulting solid was collected by filtration and washed with water (5 L). Purification by FCC, eluting with 0-20% EtOAc in CH2Cl2 gave the title compound (16.2 g, 20%) as a cream solid after trituration with diethyl ether; 1H NMR: 7.29 (1H, td), 7.74 (1H, ddd), 8.58 (1H, dt), 8.82 (1H, s), 8.98 (1H, dt), 9.10 (1H, s). m/z: ES+, MH+ 264.89.

Workup

  1. waitat 90° C. for 4 h
  2. temperatureAfter cooling
  3. stirringstirred for 0.5 h
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with water (5 L)
  6. customPurification by FCC
  7. washeluting with 0-20% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-1ecc1ebaa00d484d951866c0209a733c
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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