N,N-Dimethylglycine → 5-[3-(trifluoromethyl)-4,7-dihydropyrano[3,4-c]pyrazol-1(5H)-yl]-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

HRID 1925056노트

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HRID 1925056 반응식
I[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[CH:7]=1.CN(C)CC(O)=O.C([O-])([O-])=O.[K+].[K+].[F:42][C:43]([F:54])([F:53])[C:44]1[C:45]2[CH2:52][CH2:51][O:50][CH2:49][C:46]=2[NH:47][N:48]=1>CS(C)=O.CCOC(C)=O.[Cu]I>[F:53][C:43]([F:42])([F:54])[C:44]1[C:45]2[CH2:52][CH2:51][O:50][CH2:49][C:46]=2[N:47]([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[CH:7]=2)[N:48]=1

참가 물질

8

반응물 4

HCID 673N,N-DimethylglycineHCID 11430Potassium CarbonateHCID 509927983-(Trifluoromethyl)-1,4,5,7-tetrahydropyrano[3,4-C]pyrazoleHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

생성물 1

HCID 252531405-[3-(trifluoromethyl)-4,7-dihydropyrano[3,4-c]pyrazol-1(5H)-yl]-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione수율 5.5%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
150 °C

실험 절차

5-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione (Prep10, 150 mg, 0.282 mmol) copper (1+) iodide (59.1 mg, 0.310 mmol), N,N-dimethylglycine (32.0 mg, 0.310 mmol) and K2CO3 (86 mg, 0.620 mmol) were dissolved in Dimethyl Sulfoxide (DMSO) (2 ml) to give a light blue solution with a white precipitate. To this mixture, 3-(trifluoromethyl)-1,4,5,7-tetrahydropyrano[3,4-c]pyrazole (P38, 179 mg, 0.931 mmol) was added. After 18 h shaking at 150° C., the reaction mixture was diluted with EtOAc (5 ml) and the organic phase was washed with water (4×10 ml), then brine (5 ml), dried over Na2SO4, then filtered and the solvent evaporated. The obtained crude was passed through an SCX cartridge and eluted with 2M solution of ammonia in MeOH. The obtained mixture was iteratively purified (two times) by preparative LC-MS. The obtained fraction was passed through an SCX cartridge and eluted with 2M solution of ammonia. Obtained 8.8 mg of the title compound.

후처리

  1. customto give a light blue solution with a white precipitate
  2. washthe organic phase was washed with water (4×10 ml)
  3. dry with materialbrine (5 ml), dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe obtained crude
  7. washeluted with 2M solution of ammonia in MeOH
  8. customThe obtained mixture was iteratively purified (two times) by preparative LC-MS
  9. washeluted with 2M solution of ammonia

출처 및 근거

ORD 기록
ord-c9ac65e824b64cbca932a5d04cfd4494
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178549B2

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