Sodium hydride → HCID 56953203, compound

HRID 2366235Notes

Reaction equation

HRID 2366235 reaction equation
[CH:1]1([C:4]([NH2:6])=[O:5])[CH2:3][CH2:2]1.[H-].[Na+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=1[C:17]1[S:18][C:19]2[C:24](S(C)(=O)=O)=[N:23][CH:22]=[N:21][C:20]=2[N:29]=1>CN(C=O)C>[Cl:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([Cl:9])[C:11]=1[C:17]1[S:18][C:19]2[C:24]([NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])=[N:23][CH:22]=[N:21][C:20]=2[N:29]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80376CyclopropanecarboxamideHCID 66801895HCID 66801895, compound

Product 1

HCID 56953203HCID 56953203, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of cyclopropylcarboxamide (19 mg, 0.22 mmol) in DMF (1.5 mL) at 0° C. was added NaH (9.8 mg, 0.24 mmol). The reaction mixture was stirred at 0° C. for 10 minutes. A solution of 2-(2,6-dichlorophenyl)-7-(methylsulfonyl)thiazolo[4,5-d]pyrimidine (940 mg, 0.11 mmol) in DMF (0.5 mL) was then added at 0° C. The reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with ice-water and extracted with EtOAc (3×25 mL). The combined organic extract was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by reverse phase HPLC (Gemini-NX, 3×10 cm, gradient: 30-70% CH3CN/H2O, 0.1% NH4OH/H2O, flow rate 60 mL/min, 10 min) to give the desired compound as a yellow solid (12 mg, 31%). 1H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 8.98 (s, 1H), 7.75-7.70 (m, 2H), 7.66 (dd, J=9.4, 6.6 Hz, 1H), 2.19-2.10 (m, 1H), 0.95 (tt, J=7.6, 4.2 Hz, 4H). LCMS (Method B): RT=4.69 min, m/z: 365.0 [M+H+].

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for 2 hours
  3. customThe reaction was quenched with ice-water
  4. extractionextracted with EtOAc (3×25 mL)
  5. extractionThe combined organic extract
  6. dry with materialwas dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by reverse phase HPLC (Gemini-NX, 3×10 cm, gradient: 30-70% CH3CN/H2O, 0.1% NH4OH/H2O, flow rate 60 mL/min, 10 min)

Sources & evidence

ORD record
ord-79b992854ab34fa7a28b64b8514d83aa
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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