Hydrochloric Acid → HCID 57501750, compound

HRID 601521Notes

Reaction equation

HRID 601521 reaction equation
O[CH2:2][CH2:3][C:4]1[N:5]=[C:6]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[S:7][C:8]=1[C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([O:25][CH3:26])[CH:13]=1)=[O:10].CCN(CC)CC.CS(Cl)(=O)=O.[H-].[Na+].Cl>C(Cl)Cl>[CH3:26][O:25][C:14]1[CH:13]=[C:12]([N:11]2[CH2:2][CH2:3][C:4]3[N:5]=[C:6]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[S:7][C:8]=3[C:9]2=[O:10])[CH:17]=[CH:16][C:15]=1[O:18][C:19](=[O:24])[C:20]([CH3:22])([CH3:21])[CH3:23]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 57501722HCID 57501722, compound

Product 1

HCID 57501750HCID 57501750, compoundYield 163.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 2,2-dimethyl-propionic acid 4-{[4-(2-hydroxy-ethyl)-2-(4-methoxy-phenyl)-thiazole-5-carbonyl]-amino}-2-methoxy-phenyl ester (480 mg, 0.98 mmol) and NEt3 (177 mL, 1.27 mmol) in dry CH2Cl2 and cool to 0° C. Add dropwise methanesulfonyl chloride (98.1 mL, 1.27 mmol) and stir for 30 min. Quench the reaction mixture with saturated NH4Cl solution and extract with CH2Cl2 (3×10 mL). Dry, filter, and concentrate. Redissolve the crude material in dry DMF (6.5 mL) and chill to 0° C. Add portionwise NaH (60% dispersion, 51 mg, 1.27 mmol) then warm to ambient temperature overnight. Add 1N HCl (20 mL) and extract with EtOAc (3×10 mL). Collect insoluble solid from portioned layers via filtration. Wash the filtrate with water (40 mL), dry, filter, and concentrate. Combine the resulting material with the collected solid to give the title compound as a yellow solid (749 mg, 99%). MS (ES+) 467.3 (M+1)+. 1H NMR (400 MHz, CD3OD): δ 7.96 (d, 2H, J=8.4 Hz), 7.14 (d, 1H, J=2.2 Hz), 7.05 (d, 2H, J=8.4 Hz), 7.04 (dd, 1H, J=8.8, 2.2 Hz), 6.96 (dd, 1H, J=8.4, 2.2 Hz), 4.15 (t, 2H, J=7.0 Hz), 3.87 (s, 3H), 3.81 (s, 3H), 3.27 (t, 2H, J=7.5 Hz), 1.35 (s, 9H).

Workup

  1. customQuench the reaction mixture with saturated NH4Cl solution
  2. extractionextract with CH2Cl2 (3×10 mL)
  3. customDry
  4. filtrationfilter
  5. concentrationconcentrate
  6. dissolutionRedissolve the crude material in dry DMF (6.5 mL)
  7. temperaturechill to 0° C
  8. temperaturethen warm to ambient temperature overnight
  9. extractionextract with EtOAc (3×10 mL)
  10. filtrationCollect insoluble solid from portioned layers via filtration
  11. washWash the filtrate with water (40 mL)
  12. customdry
  13. filtrationfilter
  14. concentrationconcentrate

Sources & evidence

ORD record
ord-6becb2e6cd7444a6a06ee1d373cda01c
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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