Trifluoroacetic acid → HCID 58117093, compound

HRID 2066537Notes

Reaction equation

HRID 2066537 reaction equation
C([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][N:12]([CH2:16][C:17]3[S:25][C:24]4[C:23]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[N:22][C:21]([Cl:32])=[N:20][C:19]=4[CH:18]=3)[CH2:13]2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.[CH2:40]([N:42](CC)[CH2:43]C)C.CN(C)C(Cl)=O>C(Cl)Cl>[CH3:40][N:42]([CH3:43])[C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][N:12]([CH2:16][C:17]3[S:25][C:24]4[C:23]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[N:22][C:21]([Cl:32])=[N:20][C:19]=4[CH:18]=3)[CH2:13]2)[CH2:9]1)=[O:5]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 581170715-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester

Product 1

HCID 58117093HCID 58117093, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester (250 mg, 0.52 mmol) in DCM (4.5 mL) was added TFA (0.5 mL). The reaction mixture stirred at RT for 1 h, then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH, and concentrated in vacuo. The resultant residue was dissolved in DCM (6 mL) and triethylamine (0.48 mL, 3.28 mmol) was added. The reaction mixture was cooled to 0° C. then a solution of dimethylcarbamoyl chloride (57 μL, 0.615 mmol) in DCM (0.5 mL) was added. The reaction mixture was stirred at RT for 1 h, then partitioned between water and DCM. The organic layer was separated and washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by column chromatography to give the title compound as a colourless oil (55 mg, 24%).

Workup

  1. washThe cartridge was washed with MeOH
  2. washthen eluted with 2 M NH3 in MeOH
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in DCM (6 mL)
  5. temperatureThe reaction mixture was cooled to 0° C.
  6. stirringThe reaction mixture was stirred at RT for 1 h
  7. custompartitioned between water and DCM
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe resultant residue was purified by column chromatography

Sources & evidence

ORD record
ord-6a225aa91b7940f88575e28e8a43f67c
Source dataset
uspto-grants-2012_10
Patent number
US08293735B2

Reaction notes

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