Triethylamine → 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

HRID 17486Notes

Reaction equation

HRID 17486 reaction equation
[CH3:1][N:2]([CH3:8])[C@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.[C:16]([C:18]1[C:23]2[N:24]=[C:25]([N:27]3[CH2:30][CH:29]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:28]3)[O:26][C:22]=2[C:21](F)=[C:20]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:19]=1[CH3:46])#[N:17]>CS(C)=O>[C:16]([C:18]1[C:23]2[N:24]=[C:25]([N:27]3[CH2:28][CH:29]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:30]3)[O:26][C:22]=2[C:21]([N:5]2[CH2:6][CH2:7][C@H:3]([N:2]([CH3:8])[CH3:1])[CH2:4]2)=[C:20]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:19]=1[CH3:46])#[N:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 86630856HCID 86630856, compound

Product 1

HCID 86630855tert-Butyl (1-{4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}azetidin-3-yl)carbamateYield 53.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

(3S)-3-(Dimethylamino)pyrrolidine (180 μl, 1.42 mmol) and triethylamine (238 μl, 1.70 mmol) were added to a dimethyl sulfoxide (5 ml) solution of tert-butyl [1-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)azetidin-3-yl]carbamate (I-194) (400 mg, 0.947 mmol), followed by stirring in an oil bath at 130° C. for 3 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in chloroform (100 ml) and washed with saturated brine (100 ml). After drying over anhydrous sodium sulfate and concentration, the resulting residue was purified by silica gel column chromatography (eluent, chloroform:methanol=10:1) to obtain the entitled compound (260 mg, 53.2%) as a colorless solid.

Workup

  1. customThe reaction liquid
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in chloroform (100 ml)
  4. washwashed with saturated brine (100 ml)
  5. dry with materialAfter drying over anhydrous sodium sulfate and concentration
  6. customthe resulting residue was purified by silica gel column chromatography (eluent, chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-4a503bc31ad34059bd55bccb28d68930
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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