Acetic Anhydride → HCID 67287276, compound

HRID 1753879Notes

Reaction equation

HRID 1753879 reaction equation
[CH2:1]([S:3][C:4]1[C:9]([C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[O:11])=[C:8](C)[CH:7]=C(NC)[N:5]=1)[CH3:2].C[CH2:25][N:26]([CH:30]([CH3:32])C)[CH:27]([CH3:29])C.CC(OC(C)=O)=[O:35]>C(Cl)Cl.C1COCC1.O>[C:30]([N:26]([CH3:25])[C:27]1[N:5]=[C:4]([S:3][CH2:1][CH3:2])[C:9]([C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[O:11])=[C:8]([CH3:7])[CH:29]=1)(=[O:35])[CH3:32]

Participants

7

Reactant 3

HCID 7918Acetic Anhydride2×HCID 81531Diisopropylethylamine2×HCID 67287071HCID 67287071, compound

Product 1

HCID 67287276HCID 67287276, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 250 mg (0.75 mmol) 2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-6-(methyl-amino)-4-methyl-pyridine-3-carboxylic acid amide in DCM (5 ml) and THF (5 ml) was added 267 μl (1.58 mmol) DIPEA. At 0° C. 74 μl (0.79 mmol) acetanhydride was added dropwise and stirring was continued at RT for 16 h. Then another 297 μl (3.2 mmol) acetanhydride and 535 μl (3.2 mmol) DIPEA were added at RT and the mixture was stirred at 35° C. for 2 d. The solution was diluted with water and a 1M aq. NaOH sol. The organic layer was separated, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:2) provided 226 mg (0.6 mmol, 80%) 6-(Acetyl-methyl-amino)-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-pyridine-3-carboxylic acid amide (example 123). [M+H]+376.1

Workup

  1. customAt 0° C
  2. stirringthe mixture was stirred at 35° C. for 2 d
  3. customa 1M aq. NaOH sol. The organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by CC (hexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-d62c4cfe040d40cab62e9b42a5cd8596
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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