Trifluoroacetic acid → (1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl(3-(methylsulfinyl)-1-(5-(pyridin-2-yl)pyrimidin-2-yl)-1H-indol-6-yl)methanone

HRID 630506Notes

Reaction equation

HRID 630506 reaction equation
FC(F)(F)C(O)=O.[CH3:8][S:9]([C:11]1[C:19]2[C:14](=[CH:15][C:16]([C:20]([N:22]3[CH2:27][C@@H:26]4[CH2:28][C@H:23]3[CH2:24][N:25]4C(OC(C)(C)C)=O)=[O:21])=[CH:17][CH:18]=2)[N:13]([C:36]2[N:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=3)=[CH:38][N:37]=2)[CH:12]=1)=[O:10]>ClCCl>[C@H:23]12[CH2:28][C@H:26]([NH:25][CH2:24]1)[CH2:27][N:22]2[C:20]([C:16]1[CH:15]=[C:14]2[C:19]([C:11]([S:9]([CH3:8])=[O:10])=[CH:12][N:13]2[C:36]2[N:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=3)=[CH:38][N:37]=2)=[CH:18][CH:17]=1)=[O:21]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131735399(1S,4S)-tert-Butyl 5-(3-(methylsulfinyl)-1-(5-(pyridin-2-yl)pyrimidin-2-yl)-1H-indole-6-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 118671987(1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl(3-(methylsulfinyl)-1-(5-(pyridin-2-yl)pyrimidin-2-yl)-1H-indol-6-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4 M solution of trifluoroacetic acid in dichloromethane (5.1 mL, 20.78 mmol, 40 eq) was added at 0° C. to 244d) (0.29 g, 0.51 mmol, 1 eq) in dichloromethane (10 mL). The reaction mixture was then stirred for 3 h at room temperature. The solvent was removed under vacuum and the residue was co-distilled twice with dichloromethane, diluted with dichloromethane (50 mL) and washed with saturated potassium carbonate solution (2×20 mL) and brine (20 mL). The organic layer was dried over sodium sulfate, concentrated and finally chromatographed by preparative HPLC. White solid. Yield: 0.200 g (84% by theory)

Workup

  1. customThe solvent was removed under vacuum
  2. additiondiluted with dichloromethane (50 mL)
  3. washwashed with saturated potassium carbonate solution (2×20 mL) and brine (20 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customfinally chromatographed by preparative HPLC

Sources & evidence

ORD record
ord-493423807fc0480281e394fa252b409b
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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