Trifluoroacetic acid → HCID 136338258, compound

HRID 1529448Notes

Reaction equation

HRID 1529448 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15](C1CCCCO1)[N:14]=[C:13]2[C:25]1[CH:30]=[C:29]([O:31]CC2C=CC(OC)=CC=2)[N:28]=[C:27]([N:41]([CH3:43])[CH3:42])[N:26]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[NH:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][N:14]=[C:13]2[C:25]1[N:26]=[C:27]([N:41]([CH3:42])[CH3:43])[NH:28][C:29](=[O:31])[CH:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67959901HCID 67959901, compound

Product 1

HCID 136338258HCID 136338258, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(2,6-Difluorophenyl)-3-(2-(dimethylamino)-6-((4-methoxybenzyl)oxy)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (260 mg, 0.443 mmol) in DCM (2.0 mL) was treated with TFA, 99% (2.0 mL, 26.9 mmol) at RT and stirred at 50° for 26 h. The mixture was cooled to RT and evaporated to dryness. The residue was diluted with DCM and extracted with sat'd NaHCO3 solution. The aqueous layer was extracted with DCM 3 times, and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified with silica gel chromatography (eluting with 0-8% MeOH in DCM with 2 M NH3) to give 6-(5-((2,6-difluorophenyl)amino)-1H-indazol-3-yl)-2-(dimethylamino) pyrimidin-4(3H)-one (85 mg, 0.222 mmol, 50.2% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 383 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.90 (s, 6 H), 6.28 (br. s., 1 H), 7.05-7.25 (m, 4 H), 7.45 (d, J=8.80 Hz, 1H), 7.51 (br. s., 1 H), 7.74 (s, 1 H), 10.86 (br. s., 1 H), 13.21 (br. s., 1 H).

Workup

  1. customevaporated to dryness
  2. additionThe residue was diluted with DCM
  3. extractionextracted with sat'd NaHCO3 solution
  4. extractionThe aqueous layer was extracted with DCM 3 times
  5. dry with materialthe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified with silica gel chromatography (eluting with 0-8% MeOH in DCM with 2 M NH3)

Sources & evidence

ORD record
ord-98430b7e2aff4080942e1af525c69645
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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