Trifluoroacetic acid → N-(1-{4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}azetidin-3-yl)methanesulfonamide

HRID 17487Notes

Reaction equation

HRID 17487 reaction equation
FC(F)(F)C(O)=O.[C:8]([C:10]1[C:15]2[N:16]=[C:17]([N:19]3[CH2:22][CH:21]([NH:23]C(=O)OC(C)(C)C)[CH2:20]3)[O:18][C:14]=2[C:13]([N:31]2[CH2:35][CH2:34][C@H:33]([N:36]([CH3:38])[CH3:37])[CH2:32]2)=[C:12]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:11]=1[CH3:45])#[N:9].C(N(CC)CC)C.[CH3:53][S:54](Cl)(=[O:56])=[O:55]>ClCCl>[C:8]([C:10]1[C:15]2[N:16]=[C:17]([N:19]3[CH2:22][CH:21]([NH:23][S:54]([CH3:53])(=[O:56])=[O:55])[CH2:20]3)[O:18][C:14]=2[C:13]([N:31]2[CH2:35][CH2:34][C@H:33]([N:36]([CH3:38])[CH3:37])[CH2:32]2)=[C:12]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:11]=1[CH3:45])#[N:9]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86630855tert-Butyl (1-{4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}azetidin-3-yl)carbamate

Product 1

HCID 68584948N-(1-{4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}azetidin-3-yl)methanesulfonamideYield 20.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

With cooling with ice, trifluoroacetic acid (1 ml) was added to a dichloromethane (2 ml) solution of tert-butyl (1-{4-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}azetidin-3-yl)carbamate (I-195) (77.6 mg, 0.15 mmol), followed by stirring with cooling with ice for 1 hour. The reaction liquid was concentrated under reduced pressure, dissolved in dichloromethane (2 ml), and with cooling with ice, triethylamine (210 ml, 1.52 mmol) and methanesulfonyl chloride (25.6 μl, 0.33 mmol) were added, followed by stirring at room temperature for 1 hour. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in chloroform (50 ml), and washed with saturated brine (50 ml). After drying over anhydrous sodium sulfate and concentration, the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=10:1) to obtain the entitled compound (15.0 mg, 19.7%) as a colorless solid.

Workup

  1. temperaturewith cooling with ice for 1 hour
  2. customThe reaction liquid
  3. concentrationwas concentrated under reduced pressure
  4. dissolutiondissolved in dichloromethane (2 ml)
  5. additionwere added
  6. stirringby stirring at room temperature for 1 hour
  7. customThe reaction liquid
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in chloroform (50 ml)
  10. washwashed with saturated brine (50 ml)
  11. dry with materialAfter drying over anhydrous sodium sulfate and concentration
  12. customthe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-0ad52c744dad4e6188c33cbdc5b39e95
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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