Trifluoroacetic acid → HCID 89462643, compound

HRID 1473224Notes

Reaction equation

HRID 1473224 reaction equation
C([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:22][C:23]([O:25]C(C)(C)C)=O)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)[C:7]([O:9][CH3:10])=[O:8])(C)(C)C.[C:37](O)([C:39]([F:42])(F)F)=O.C(OC(C)(C)C)(C)(C)C.FC1C=[CH:59][C:57]([NH2:58])=[CH:56][CH:55]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O.C(OCC)(=O)C>[F:42][C:39]1[CH:37]=[CH:59][C:57]([NH:58][C:23](=[O:25])[CH2:22][N:19]2[C:14]3[C:15](=[O:18])[N:16]([CH3:17])[C:11]([CH:6]([OH:5])[C:7]([O:9][CH3:10])=[O:8])=[C:12]([C:30]4[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=4)[C:13]=3[CH:21]=[CH:20]2)=[CH:56][CH:55]=1

Participants

10

Reactant 6

HCID 6422Trifluoroacetic acidHCID 97314-FluoroanilineHCID 22541Di-tert-butyl etherHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89462880HCID 89462880, compound

Product 1

HCID 89462643HCID 89462643, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of methyl 2-(tert-butoxy)-2-(1-(2-(tert-butoxy)-2-oxoethyl)-6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (49 mg, 0.099 mmol) in Dichloromethane (DCM) (2.0 mL) and TFA (0.4 mL, 0.102 mmol) was stirred at ambient temperature for 60 hours (a dark mixture resulted). LCMS indicated cleavage of both t-butyl ester as well as t-butyl ether. The mixture was concentrated and then used crude in the next step. A mixture of the crude residue, 4-fluoroaniline (0.014 mL, 0.150 mmol) and Hünig's base (0.054 mL, 0.306 mmol) in N,N-Dimethylformamide (DMF) (0.5 mL) was treated with HATU (62.0 mg, 0.163 mmol) and then stirred at ambient temperature for 10 minutes. The mixture was diluted with ethyl acetate, washed with water, then brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% Ethyl acetate/hexanes) to give the impure amide product as a pale yellow residue (20.5 mg, 42% yield). LC/MS (m/z) ES+=497 (M+1).

Workup

  1. customresulted)
  2. concentrationThe mixture was concentrated
  3. stirringstirred at ambient temperature for 10 minutes
  4. washwashed with water
  5. dry with materialbrine, dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel (0-70% Ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-50ca9089da324f1f9bd2c52d0a20e32a
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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