tert-Butylsulfinamide, (S)-(-)- → tert-butyl 4-[5-[(Z)-N-[(S)-tert-butylsulfinyl]-C-(4-fluorophenyl)carbonimidoyl]pyrimidin-2-yl]piperazine-1-carboxylate

HRID 522695Notes

Reaction equation

HRID 522695 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([C:8]2[CH:9]=[N:10][C:11]([N:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)=[N:12][CH:13]=2)=O)=[CH:4][CH:3]=1.[CH3:29][C:30]([S@@:33]([NH2:35])=[O:34])([CH3:32])[CH3:31]>C1COCC1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[C:30]([S@@:33](/[N:35]=[C:6](/[C:5]1[CH:27]=[CH:28][C:2]([F:1])=[CH:3][CH:4]=1)\[C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[N:12][CH:13]=1)=[O:34])([CH3:32])([CH3:31])[CH3:29]

Participants

7

Reactant 2

HCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 118023371HCID 118023371, compound

Product 1

HCID 118023121tert-butyl 4-[5-[(Z)-N-[(S)-tert-butylsulfinyl]-C-(4-fluorophenyl)carbonimidoyl]pyrimidin-2-yl]piperazine-1-carboxylateYield 66%

Reagents, catalysts & solvents 4

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of tert-butyl 4-(5-(4-fluorobenzoyl)pyrimidin-2-yl)piperazine-1-carboxylate (4.0 g, 10.4 mmol), (S)-2-methylpropane-2-sulfinamide (2.5 g, 20.7 mmol) in THF (60 mL) was added titanium ethoxide (20 mL) at room temperature. The resultant solution was heated at 70° C. overnight. After that, the reaction was cooled to room temperature, diluted with ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (500 mL). The mixture was filtered through Celite. The filtrate was separated. Aqueous layer was extracted with ethyl acetate (200 mL×3). Then organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column (petroleum ether:ethyl acetate 2:1) to afford the title compound (3.3 g, yield 66%) as a yellow solid. MS (ES+) requires: 489, found 490 [M+H]+; purity: 95% (UV at 254 nm).

Workup

  1. filtrationThe mixture was filtered through Celite
  2. customThe filtrate was separated
  3. extractionAqueous layer was extracted with ethyl acetate (200 mL×3)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate 2:1)

Sources & evidence

ORD record
ord-e42f4e5989f54bc9b97b4e8ae1409cc4
Source dataset
uspto-grants-2016_05
Patent number
US09334263B2

Reaction notes

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