Cesium carbonate → HCID 66851519, compound

HRID 1466658Notes

Reaction equation

HRID 1466658 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.I[CH:28]1[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[NH:30]1[CH2:31][CH:28]([N:10]2[CH:11]=[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][CH3:26])=[N:9]2)[CH2:29]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 178490635HCID 178490635, compound

Product 1

HCID 66851519HCID 66851519, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of N-(3-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (50.0 mg, 0.136 mmol, 1 equiv), tert-butyl 3-iodoazetidine-1-carboxylate (230.3 mg, 0.813 mmol, 6.00 equiv), and cesium carbonate (177 mg, 0.542 mmol, 4.00 equiv) in N,N-dimethylformamide (1 mL) was heated at 50° C. After 5 h, the reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL). The aqueous layer was extracted with ethyl acetate (2×5 mL). The combined organic was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude residue was dissolved in dichloromethane (2 mL) and trifluoroacetic acid (2 mL) at 24° C. After 5 h, the reaction mixture was concentrated in vacuo and purified by preparative HPLC to afford product (12.7 mg, 22% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.75 (s, 1H), 9.36 (m, 1H), 8.79 (m, 1H), 8.67 (s, 1H), 8.46 (s, 1H), 7.53-7.56 (m, 2H), 7.29-7.34 (m, 2H), 5.45 (m, 1H), 4.33 (m, 2H), 4.23 (m, 2H), 3.86 (s, 3H). LCMS (ESI): M+H=424.1.

Workup

  1. customthe reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×5 mL)
  3. dry with materialThe combined organic was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude residue was dissolved in dichloromethane (2 mL)
  7. customat 24° C
  8. waitAfter 5 h
  9. concentrationthe reaction mixture was concentrated in vacuo
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-9bf8a8abb6754601aeec0693db1e4635
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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