Trifluoroacetic acid → Ammonia methanol

HRID 1957938Notes

Reaction equation

HRID 1957938 reaction equation
[NH2:1][C:2]([C@H]1[C@H]2C[C@H](C=C2)[C@H]1[NH:11][C:12]1[C:17](F)=[CH:16][N:15]=[C:14]([NH:19]C2C=CC(N3CCN(C)CC3)=C(C)C=2)[N:13]=1)=[O:3].C(O)(C(F)(F)F)=O>CO>[NH3:1].[CH3:2][OH:3].[NH2:19][C:14]1[N:13]=[C:12]([NH2:11])[CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11569967Cenisertib

Product 2

HCID 674312,4-DiaminopyrimidineHCID 21705897Ammonia methanolYield 2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A sealed tube charged with enantiomerically pure mono-SNAr product 57a (2.25 g, 8 mmol), aniline 7 (1.80 g, 8.8 mmol), TFA (1.12 mL) and methanol (18 mL) was stirred at 100° C. for 24 hours. The resulting viscous but homogeneous solution was concentrated and the residue was chromatographed (silica gel, CH2Cl2 then 2-5% 2N NH3/MeOH in CH2Cl2) to afford the expected 2,4-diaminopyrimidine derivative 60a (2.28 g, 63%; purity: 95% AUC; enantiomeric purity: greater than 99% as determined by chiral HPLC. The chiral analytical data, 1H NMR and LCMS analyses were found to be identical with the enantiomer designated E1; [α]DRT +44.4° (c 1.0, MeOH).

Workup

  1. concentrationThe resulting viscous but homogeneous solution was concentrated
  2. customthe residue was chromatographed (silica gel, CH2Cl2

Sources & evidence

ORD record
ord-82953a9268594a05b049fba134a68de1
Source dataset
uspto-grants-2013_04
Patent number
US08410093B2

Reaction notes

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