Dimethyl Sulfoxide → 4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]N-(2-hydroxyethyl)-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

HRID 17389

Reaction equation

HRID 17389 reaction equation
CS(C)=O.[CH3:5][N:6]([CH3:12])[C@@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1.[O:13]([CH2:31][CH2:32][N:33]([CH3:55])[C:34]([C:36]1[O:37][C:38]2[C:44](F)=[C:43]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:42]([CH3:52])=[C:41]([C:53]#[N:54])[C:39]=2[N:40]=1)=[O:35])[Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[Cl-].[Na+].O>[C:53]([C:41]1[C:39]2[N:40]=[C:36]([C:34]([N:33]([CH2:32][CH2:31][OH:13])[CH3:55])=[O:35])[O:37][C:38]=2[C:44]([N:9]2[CH2:10][CH2:11][C@H:7]([N:6]([CH3:12])[CH3:5])[CH2:8]2)=[C:43]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:42]=1[CH3:52])#[N:54]

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 68584854N-[2-(tert-Butyldiphenylsiloxy)ethyl]-4-cyano-7-fluoro-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685869954-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]N-(2-hydroxyethyl)-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Under nitrogen atmosphere, a dimethyl sulfoxide (1 ml) solution of (3R)-3-(dimethylamino)pyrrolidine (76 μl, 598 μmol) was added at 150° C. to a dimethyl sulfoxide (9 ml) solution of N-[2-(tert-butyldiphenylsiloxy)ethyl]-4-cyano-7-fluoro-N,5-dimethyl-6-phenyl-1,3-benzoxazole-2-carboxamide (I-124) (295 mg, 499 μmol) and triethylamine (90 μl, 649 μmol), followed by stirring at the same temperature for 20 minutes. After pooling, saturated brine was added to the reaction liquid, and the reaction liquid was extracted with ethyl acetate. Next, the combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the eluate with dichloromethane/methanol (10:1, v/v) gave the entitled compound (93 mg, 42%) as an amorphous substance.

Workup

  1. customthe reaction liquid
  2. extractionwas extracted with ethyl acetate
  3. washNext, the combined organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d46b01018cac494cac306828d245f9ae
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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