Trifluoroacetic acid → HCID 68325484, compound

HRID 2403320Notes

Reaction equation

HRID 2403320 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]2[O:23][CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[N:14]=[CH:13][C:12]([CH:15]2[CH2:17][CH2:16]2)=[CH:11][N:10]=1.FC(F)(F)C(O)=O.CCOC(C)=O.C1COCC1>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]2[O:23][CH2:22][CH2:21][NH:20][CH2:19]2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][C:12]([CH:15]2[CH2:17][CH2:16]2)=[CH:13][N:14]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 21939870Tetrahydrofuran ethyl acetateHCID 86671407HCID 86671407, compound

Product 1

HCID 68325484HCID 68325484, compoundYield 104.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of tert-butyl (RS)-2-(3-chloro-4-(5-cyclopropylpyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate (35 mg) in acetonitrile (1.5 ml) and water (4.5 ml) was added trifluoroacetic acid (77.3 μl). The reaction mixture was then capped and the mixture was shaken at 80° C. for 3 h. The reaction mixture was then cooled to room temperature and poured into EtOAc/THF (1:1) and washed with 1 M aq. NaOH. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis; gradient: heptane/EtOAc/MeOH) to afford (RS)—N-(2-chloro-4-(morpholin-2-yl)phenyl)-5-cyclopropylpyrimidin-2-amine (28 mg, 76%) as a white solid. MS (ISP): 333.1 ([{37Cl}M+H]+), 331.1 ([{35Cl}M+H]+).

Workup

  1. customThe reaction mixture was then capped
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. washwashed with 1 M aq. NaOH
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis; gradient: heptane/EtOAc/MeOH)

Sources & evidence

ORD record
ord-74cb0960a0c541af82513152f9684916
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

Loading…