N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide → HCID 25182146, compound

HRID 2077491Notes

Reaction equation

HRID 2077491 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:20]=[CH:19][C:11]3[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=3[CH:9]=2)[CH:5]=[CH:4][N:3]=1.[Br-].[CH2:22]([Zn+])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([C:2]1[N:7]=[C:6]([C:8]2[CH:20]=[CH:19][C:11]3[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=3[CH:9]=2)[CH:5]=[CH:4][N:3]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 51357685N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamideHCID 178419772HCID 178419772, compound3×

Product 1

HCID 25182146HCID 25182146, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (59.0 mg, 194 μmol) was suspended in THF (1.8 mL) to which tetrakis(triphenylphosphine)palladium (25.6 mg, 22 μmol) and benzylzinc bromide, 0.5 m solution in THF (0.55 mL, 275 μmol) were added under argon, and the reaction solution was stirred at RT. After about 2 hours, the reaction was heated to 80° C., and stirring was continued under argon. After about 100 minutes, additional Pd(PPh3)4 (21 mg) and benzylzinc bromide (0.57 mL) were added, and the reaction was stirred. After another hour or so, additional benzylzinc bromide (0.73 mL) was added, and stirring was continued at 80° C. The reaction was stirred overnight and quenched with saturated ammonium chloride (1.5 mL) and 0.5 M EDTA (2.5 mL), extracted with 10:1 DCM/MeOH, and the organic phases were dried over sodium sulfate, filtered through Celite®(diatomaceous earth), and concentrated. The crude concentrate was purified on a silica gel column (20:1 to >5:1 DCM/MeOH), and the product-containing fractions were collected, concentrated, and washed with Et2O and MeOH and filtered. The solid was collected and purified on HPLC (10% to >95% MeCN/water with 0.1% TFA over 40 minutes), to provide N-(6-(2-benzylpyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (8 mg, 11% yield). MS (ESI pos. ion) m/z: 361. Calculated exact mass for C20H16N4OS: 360. 1H NMR (400 MHz, DMSO-d6): 12.50 (s, 1H), 8.85 (s, 1H), 8.78 (d, J=5.5 Hz, 1H), 8.29 (d, J=8.0 Hz, 1H), 7.95 (d, J=5.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.38 (m, 2H), 7.31 (m, 2H), 7.21 (m, 1H), 4.28 (s, 2H), 2.23 (s, 3H).

Workup

  1. additionwere added under argon
  2. temperaturethe reaction was heated to 80° C.
  3. stirringstirring
  4. waitAfter about 100 minutes
  5. stirringthe reaction was stirred
  6. waitAfter another hour
  7. stirringstirring
  8. customwas continued at 80° C
  9. stirringThe reaction was stirred overnight
  10. customquenched with saturated ammonium chloride (1.5 mL) and 0.5 M EDTA (2.5 mL)
  11. extractionextracted with 10:1 DCM/MeOH
  12. dry with materialthe organic phases were dried over sodium sulfate
  13. filtrationfiltered through Celite®(diatomaceous earth), and
  14. concentrationconcentrated
  15. concentrationThe crude concentrate
  16. customwas purified on a silica gel column (20:1 to >5:1 DCM/MeOH)
  17. customthe product-containing fractions were collected
  18. concentrationconcentrated
  19. washwashed with Et2O and MeOH
  20. filtrationfiltered
  21. customThe solid was collected
  22. custompurified on HPLC (10% to >95% MeCN/water with 0.1% TFA over 40 minutes)

Sources & evidence

ORD record
ord-5ff646f026494485b44edd9fd813e41c
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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