Trifluoroacetic acid → 2-(2-(2-(2-((1-(Azetidin-3-yl)-1H-pyrazol-4-yl)-amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1779090Notes

Reaction equation

HRID 1779090 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:43])[CH2:10][C:11]1[CH:42]=[CH:41][CH:40]=[CH:39][C:12]=1[CH2:13][CH2:14][C:15]1[C:20]([CH3:21])=[CH:19][N:18]=[C:17]([NH:22][C:23]2[CH:24]=[N:25][N:26]([CH:28]3[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29]3)[CH:27]=2)[N:16]=1>C(Cl)Cl>[NH:30]1[CH2:29][CH:28]([N:26]2[CH:27]=[C:23]([NH:22][C:17]3[N:16]=[C:15]([CH2:14][CH2:13][C:12]4[CH:39]=[CH:40][CH:41]=[CH:42][C:11]=4[CH2:10][C:9]([NH2:8])=[O:43])[C:20]([CH3:21])=[CH:19][N:18]=3)[CH:24]=[N:25]2)[CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712726tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 730557502-(2-(2-(2-((1-(Azetidin-3-yl)-1H-pyrazol-4-yl)-amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamideYield 1.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL) was added to a solution of tert-butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate (A120) (0.050 g, 0.102 mmol) in DCM (3 mL) and the resulting mixture stirred at room temperature for 3 hours. The volatiles were removed under reduced pressure then 2 M aqueous K2CO3 (5 mL) and water (15 mL) were added to the residue. The resulting aqueous solution was extracted with EtOAc (3×15 mL) then the combined organic extracts were dried (MgSO4), filtered, evaporated in vacuo and adsorbed onto silica gel. The product was purified using column chromatography (CombiFlash Rf, 4 g SiO2 Cartridge, 5-50% MeOH in DCM) to give the title compound 30 as a yellow oil (0.6 mg, 1.5%); 1H NMR (300 MHz, d4-MeOH) δ 8.08 (d, J=2.0 Hz, 2H), 7.66 (s, 1H), 7.18-7.26 (m, 4H), 5.19-5.26 (m, 1H), 4.67 (t, J=9.0 Hz, 1H), 4.54 (dd, J=9.4, 5.3 Hz, 1H), 4.56 (t, J=9.8 Hz, 1H), 4.30 (dd, J=10.4, 5.5 Hz, 1H), 3.65 (s, 2H), 3.14 (t, J=2.9 Hz, 2H), 2.98-3.01 (m, 2H), 1.93 (s, 3H). LCMS-B: rt 4.426 min; m/z 392 [M+H]+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. addition2 M aqueous K2CO3 (5 mL) and water (15 mL) were added to the residue
  3. extractionThe resulting aqueous solution was extracted with EtOAc (3×15 mL)
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe product was purified

Sources & evidence

ORD record
ord-00d6058d84bf4db083a146e6910b1fc0
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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