Trifluoroacetic acid → HCID 86708701, compound

HRID 921800Notes

Reaction equation

HRID 921800 reaction equation
[Si:1]([O:8][CH:9]1[CH:13]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH2:12][N:11]([C:21]([C:23]2[C:24]([Cl:39])=[C:25]([NH:31]C(=O)OC(C)(C)C)[CH:26]=[C:27]([C:29]#[N:30])[CH:28]=2)=[O:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[NH2:31][C:25]1[CH:26]=[C:27]([CH:28]=[C:23]([C:21]([N:11]2[CH2:12][CH:13]([N:14]3[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]3)[CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10]2)=[O:22])[C:24]=1[Cl:39])[C:29]#[N:30]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86708700HCID 86708700, compound

Product 1

HCID 86708701HCID 86708701, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(+/−)-tert-butyl (3-(3-((tert-butyldimethylsilyl)oxy)-4-(4-methylpiperazin-1-yl)pyrrolidine-1-carbonyl)-2-chloro-5-cyanophenyl)carbamate (120 mg, 0.208 mmol) was treated with TFA (25% in 1,2-dichloroethane, 2 mL, 6.49 mmol) at room temperature for 1 h. The reaction mixture was diluted with dichloromethane and washed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 1-7.5% methanol/dichloromethane). (+/−)-3-amino-5-(3-((tert-butyldimethylsilyl)oxy)-4-(4-methylpiperazin-1-yl)pyrrolidine-1-carbonyl)-4-chlorobenzonitrile (86 mg) was obtained as a brown oil.

Workup

  1. washwashed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customthe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (40 g column, eluting with 1-7.5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-860da1437cab42bab75544b7e12aec19
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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