Trifluoroacetic acid → 4-fluoro-N-{2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-3-trifluoromethyl-benzamide

HRID 550830

반응식

HRID 550830 반응식
C(O[C:6](=[O:25])[NH:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][C:14]1[S:15][C:16]2[N:17]=[CH:18][N:19]=[C:20]([O:23][CH3:24])[C:21]=2[N:22]=1)=[O:12])(C)(C)C.FC(F)(F)C(O)=O.COC1C2N=C(NC(N3CCC(N)C3)=O)SC=2N=CN=1.[F:53][C:54]1[CH:62]=[CH:61][C:57](C(Cl)=O)=[CH:56][C:55]=1[C:63]([F:66])([F:65])[F:64]>C(Cl)Cl>[F:53][C:54]1[CH:62]=[CH:61][C:57]([C:6]([NH:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][C:14]2[S:15][C:16]3[N:17]=[CH:18][N:19]=[C:20]([O:23][CH3:24])[C:21]=3[N:22]=2)=[O:12])=[O:25])=[CH:56][C:55]=1[C:63]([F:64])([F:65])[F:66]

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acid2회HCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 59011968{2-[3-(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-carbamic acid tert-butyl esterHCID 724893723-Amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

생성물 1

HCID 248304504-fluoro-N-{2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-3-trifluoromethyl-benzamide수율 11.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

A solution of {2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-carbamic acid tert-butyl ester (170 mg, 0.46 mmol) was treated with trifluoroacetic acid (80 μL, 0.57 mmol). The reaction was stirred at 25° C. for 1 h. The reaction was then concentrated in vacuo, triturated with diethyl ether, collected by filtration and dried in vacuo. A portion of the resulting trifluoroacetic acid salt of 3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (88 mg, 0.23 mmol) in methylene chloride at 25° C. was treated with 4-fluoro-3-(trifluoromethyl)benzoyl chloride (70 mL, 0.46 mmol). The resulting solution was stirred at 25° C. overnight. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 3:1 ethyl acetate/hexanes to 100% ethyl acetate) afforded 4-fluoro-N-{2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-3-trifluoromethyl-benzamide (25 mg, 11.8%) as a white solid; ES-HRMS m/e calcd for C17H14F4N6O3S (M+H)+ 459.0857, found 459.0862.

후처리

  1. concentrationThe reaction was then concentrated in vacuo
  2. customtriturated with diethyl ether
  3. filtrationcollected by filtration
  4. customdried in vacuo
  5. stirringThe resulting solution was stirred at 25° C. overnight
  6. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 3:1 ethyl acetate/hexanes to 100% ethyl acetate)

출처 및 근거

ORD 기록
ord-25c21f53190f4b0989a1dd0ae00e1973
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947692B2

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