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

HRID 550830Notes

Reaction equation

HRID 550830 reaction equation
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]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-25c21f53190f4b0989a1dd0ae00e1973
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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