N,N-Dimethylglycine → HCID 25253141, compound

HRID 1925058Notes

Reaction equation

HRID 1925058 reaction equation
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:52]2[CH2:51][CH2:50][CH2:49][CH2:48][C:47]=2[NH:46][N:45]=1>CS(C)=O.CCOC(C)=O.[Cu]I>[F:24][C:23]([F:26])([F:25])[C:20]1[CH:21]=[CH:22][C:17]([C@:13]23[CH2:14][C@H:15]2[CH2:16][N:11]([CH2:10][CH2:9][CH2:8][N:6]2[CH:7]=[C:2]([N:46]4[C:47]5[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=5[C:44]([C:43]([F:42])([F:54])[F:53])=[N:45]4)[C:3](=[O:28])[NH:4][C:5]2=[O:27])[CH2:12]3)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 11430Potassium CarbonateHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 25253141HCID 25253141, compoundYield 4.99%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

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)-4,5,6,7-tetrahydro-1H-indazole (commercially available from ABCR, 177 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 in MeOH. 9.4 mg (4.99% yield) of the title compound were obtained.

Workup

  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 in MeOH

Sources & evidence

ORD record
ord-22fa83453d64409885cca080b10f60f9
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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