Triethylamine → N-{7-cyano-6-[3-({[5-(trifluoromethyl)pyridin-2-yl]carbamoyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamide

HRID 1097527Notes

Reaction equation

HRID 1097527 reaction equation
[C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:35]=[CH:36][CH:37]=1)[O:17][C:18]1[CH:32]=[CH:31][C:21]2[N:22]=[C:23]([NH:25][C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])[S:24][C:20]=2[C:19]=1[C:33]#[N:34].C(N(CC)CC)C.[F:45][C:46]([F:55])([F:54])[C:47]1[CH:48]=[CH:49][C:50]([NH2:53])=[N:51][CH:52]=1>O1CCCC1.C(OCC)(=O)C>[C:33]([C:19]1[C:20]2[S:24][C:23]([NH:25][C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])=[N:22][C:21]=2[CH:31]=[CH:32][C:18]=1[O:17][C:16]1[CH:35]=[CH:36][CH:37]=[C:14]([NH:13][C:1](=[O:12])[NH:53][C:50]2[CH:49]=[CH:48][C:47]([C:46]([F:54])([F:45])[F:55])=[CH:52][N:51]=2)[CH:15]=1)#[N:34]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 86644685N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 59454504N-{7-cyano-6-[3-({[5-(trifluoromethyl)pyridin-2-yl]carbamoyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamideYield 104.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of bis(trichloromethyl) carbonate (59.3 mg, 0.200 mmol) in tetrahydrofuran (2 mL) were added N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (200 mg, 0.571 mmol) produced in Example 3(vi) and triethylamine (158 μL, 1.14 mmol) at 4° C., and the mixture was stirred at the same temperature for 30 min. 5-(Trifluoromethyl)pyridin-2-amine (185 mg, 1.14 mmol) was added to the reaction mixture, and the mixture was stirred at 50° C. for 2 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), washed successively with saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→10/90), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-heptane (1/1) to give the title compound (113 mg, 37%) as a white powder.

Workup

  1. stirringthe mixture was stirred at 50° C. for 2 hr
  2. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationInsoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→10/90)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate/n-heptane (1/1)

Sources & evidence

ORD record
ord-563eb13baad54c5981175e4fda09442d
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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