Water → HCID 19039964, compound

HRID 1684623Notes

Reaction equation

HRID 1684623 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:22]=1)[CH2:7][CH:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:19])[CH:15]=2)[O:10][C:9]1([CH3:21])[CH3:20].[H-].[Na+].Cl[CH2:28][C:29]1[S:30][C:31]2[CH:37]=[C:36]([F:38])[C:35]([F:39])=[CH:34][C:32]=2[N:33]=1.O>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:22]=1)[CH2:7][CH:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH2:28][C:29]3[S:30][C:31]4[CH:37]=[C:36]([F:38])[C:35]([F:39])=[CH:34][C:32]=4[N:33]=3)[CH:15]=2)[O:10][C:9]1([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 19039914HCID 19039914, compoundHCID 19039940HCID 19039940, compound

Product 1

HCID 19039964HCID 19039964, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2.36 (7.21 mmole) of the product of Example 102 in 25 mL DMF at 0° C. was added 332 mg (8.29 mmole) 60% sodium hydride. The mixture was stirred at 0° C. then a solution of 2.06 g (9.37 mmole) 2-(chloromethyl)-5,6-difluorobenzothiazole in 15 mL DMF was added dropwise. The mixture was slowly warmed to room temperature and stirred for 18 hours. The mixture was poured into water and then extracted with ethyl acetate. The ethyl acetate extract was washed successively with 1N KOH, water and brine and then dried (MgSO4) and concentrated to give an oil. Flash chromatography on silica gel eluting with 50% ethyl acetate in hexanes gave 2.3 g (62%) of the title product as a solid. NMR (CDCl3): δ1.45 (d, 6H); 2.90 (m, 3H); 3.69 (s, 3H); 5.39 (s, 2H). MS (Cl, NH3) m/e: 528 (M+ +18), 511 (M+ +1,100).

Workup

  1. temperatureThe mixture was slowly warmed to room temperature
  2. stirringstirred for 18 hours
  3. extractionextracted with ethyl acetate
  4. extractionThe ethyl acetate extract
  5. washwas washed successively with 1N KOH, water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto give an oil

Sources & evidence

ORD record
ord-cbb4878fe7a14262a210e415eff7d74c
Source dataset
uspto-grants-1997_06
Patent number
US05641789

Reaction notes

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