Hydrochloric Acid → N-{5-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

HRID 1157610Notes

Reaction equation

HRID 1157610 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:32][CH3:33])=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:34][N:35]([CH3:46])[CH:36]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[C:41]([NH2:45])[CH:42]=2)[CH2:37]1.Cl>CC(O)C>[CH3:34][N:35]([CH3:46])[CH:36]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[C:41]([NH:45][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[CH:19][C:20]([O:32][CH3:33])=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]6[S:27][CH:28]=[CH:29][CH:30]=6)[CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:42]=2)[CH2:37]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 54309634HCID 54309634, compoundHCID 57737232N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

Product 1

HCID 16749889N-{5-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamideYield 24%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide (90 mg, 0.19 mmol) in anhydrous i-PrOH (3 mL) was added N2,N2-dimethylindane-2,5-diamine (37 mg, 0.21 mmol) followed by catalytic 12M HCl. After heating for 10 min. in the microwave at 180° C., the reaction was quenched with saturated NaHCO3 (25 mL) and the solvent was removed by rotary evaporation. The aqueous layer was extracted with DCM (25 mL), the organic layer-concentrated, and purified by column chromatography (1-10% MeOH in DCM) to provide the product (27 mg, 24%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.18 (s, 6H), 2.65-2.71 (m, 2H), 2.88-2.97 (m, 2H), 3.89 (s, 3H), 3.98 (s, 2H), 6.51 (d, 1H, J=5.3 Hz), 6.94-6.96 (m, 2H), 7.02-7.14 (m, 3H), 7.26-7.28 (m, 1H), 7.35-7.43 (m, 3H), 7.63 (s, 1H), 8.20 (d, 1H, J=5.3 Hz), 8.31 (s, 1H), 8.43 (d, 1H, J=8.9 Hz), 8.79 (d, 1H, J=7.0 Hz) 9.38 (s, 1H), 9.45 (s, 1H) ppm. ES-LC/MS m/z=616 [M+H]+.

Workup

  1. customthe reaction was quenched with saturated NaHCO3 (25 mL)
  2. customthe solvent was removed by rotary evaporation
  3. extractionThe aqueous layer was extracted with DCM (25 mL)
  4. customthe organic layer-concentrated, and purified by column chromatography (1-10% MeOH in DCM)

Sources & evidence

ORD record
ord-f926c9a1d69341e9a6f0b36aff26391f
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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