Triethylamine → Ethyl 2-{4-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}-1,3-thiazole-4-carboxylate

HRID 17491Notes

Reaction equation

HRID 17491 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]([C:27]3[S:28][CH:29]=[C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:31]=3)[O:26][C:22]=2[C:21](F)=[C:20]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:19]=1[CH3:44])#[N:17]>CS(C)=O>[C:16]([C:18]1[C:23]2[N:24]=[C:25]([C:27]3[S:28][CH:29]=[C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:31]=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:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:19]=1[CH3:44])#[N:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 68584336Ethyl 2-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)-1,3-thiazole-4-carboxylate

Product 1

HCID 68585881Ethyl 2-{4-cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazol-2-yl}-1,3-thiazole-4-carboxylateYield 66.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

(3S)-3-(Dimethylamino)pyrrolidine (91.6 μl, 0.722 mmol) and triethylamine (101 μl, 0.722 mmol) were added to a dimethyl sulfoxide (2 ml) solution of ethyl 2-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)-1,3-thiazole-4-carboxylate (I-197) (147 mg, 0.361 mmol), followed by stirring in an oil bath at 100° C. for 3 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in chloroform (100 ml) and washed with water (50 ml) and saturated brine (50 ml). After drying over anhydrous sodium sulfate and concentration, the resulting residue was purified by silica gel column chromatography (eluent, chloroform:methanol=100:1→100:3), and the obtained yellow solid was purified in slurry with isopropanol (3 ml) to obtain the entitled compound (120 mg, 66.3%) as a pale yellow solid.

Workup

  1. customThe reaction liquid
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in chloroform (100 ml)
  4. washwashed with water (50 ml) and saturated brine (50 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=100:1→100:3)
  7. customthe obtained yellow solid was purified in slurry with isopropanol (3 ml)

Sources & evidence

ORD record
ord-266c492b756d4518a924fad325b2acb5
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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