Pyridine → 3,3-dimethyl-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2,3-dihydrobenzofuran-6-carboxamide

HRID 1409252Notes

Reaction equation

HRID 1409252 reaction equation
[CH3:1][C:2]1([CH3:14])[C:6]2[CH:7]=[CH:8][C:9]([C:11](Cl)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3]1.N1C=CC=CC=1.[CH3:21][C:22]1[CH:37]=[C:25]2[N:26]=[C:27]([NH2:36])[CH:28]=[C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:24]2[N:23]=1>C(#N)C.O>[CH3:1][C:2]1([CH3:14])[C:6]2[CH:7]=[CH:8][C:9]([C:11]([NH:36][C:27]3[CH:28]=[C:29]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[N:24]4[N:23]=[C:22]([CH3:21])[CH:37]=[C:25]4[N:26]=3)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 582071812-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amineHCID 866522793,3-Dimethyl-2,3-dihydrobenzofuran-6-carbonyl chloride

Product 1

HCID 670643233,3-dimethyl-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2,3-dihydrobenzofuran-6-carboxamideYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a 25 ml pear flask containing crude 3,3-dimethyl-2,3-dihydrobenzofuran-6-carbonyl chloride (25 mg, 0.12 mmol) was added pyridine (1 mL), immediately followed by 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 26.9 mg, 0.120 mmol). The mixture was stirred at room temperature for ˜16 h. The reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate, and the aqueous layer was extracted one more time with ethyl acetate. Combined organic layers were washed once more with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by SiO2 (20% EtOAc, second spot from the top) to give an off-white solid. To facilitate transfer of the small amount of product, the solid was dissolved in 0.5 mL of acetonitrile, and then suspended in 15 mL of water. Lyophilization of the mixture gave the titled product (5.1 mg, 11% yield). 1H NMR (CHLOROFORM-d) δ: 8.58 (s, 1H), 8.08-8.15 (m, 3H), 7.53-7.59 (m, 3H), 7.46 (dd, J=7.7, 1.6 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 6.28 (s, 1H), 4.31-4.34 (m, 2H), 2.50 (s, 3H), 1.36-1.42 (m, 6H); ESI-MS: m/z 399.4 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  2. extractionthe aqueous layer was extracted one more time with ethyl acetate
  3. washCombined organic layers were washed once more with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by SiO2 (20% EtOAc, second spot from the top)
  8. customto give an off-white solid

Sources & evidence

ORD record
ord-233142b248f9416d8041203aaec86d1e
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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