Trifluoroacetic acid → HCID 178506386, compound

HRID 77456Notes

Reaction equation

HRID 77456 reaction equation
O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([O:16][CH2:17][C:18]3[CH:19]=[N:20][C:21]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=4)=[N:22][CH:23]=3)=[CH:13][CH:14]=2)[C:9]([C:36]([F:39])([F:38])[F:37])=[N:8]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:35][C:32]([F:33])([F:34])[O:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:21]2[N:22]=[CH:23][C:18]([CH2:17][O:16][C:12]3[CH:11]=[C:10]4[C:15](=[CH:14][CH:13]=3)[NH:7][N:8]=[C:9]4[C:36]([F:38])([F:39])[F:37])=[CH:19][N:20]=2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866797415-(((1-(tetrahydro-2H-pyran-2-yl)-3-(trifluoromethyl)-1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine

Product 1

HCID 178506386HCID 178506386, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(((1-(tetrahydro-2H-pyran-2-yl)-3-(trifluoromethyl)-1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (0.03 g, 0.054 mmol) in DCM (5 mL) at 0° C., TFA (2 mL, 26.0 mmol) was added. The reaction mixture was stirred at room temperature for 5 h. Solvent was removed under vacuum and the crude product was purified by preparative HPLC on an Inertsil ODS column (19×250 mm, 5μ) using 0-65% mobile phase B (ACN) in mobile phase A (0.1% TFA) over 6 min to give N-(4-(trifluoromethoxy)phenyl)-5-(((3-(trifluoromethyl)-1H-indazol-5-yl)oxy)methyl)pyrimidin-2-amine as an off-white solid (10 mg, 39%). 1HNMR 400 MHz, DMSO-d6: δ ppm 5.11 (s, 1H), 7.22-7.22 (m, 1H), 7.29-7.30 (m, 3H), 7.65 (d, J=9.20 Hz, 1H), 7.86-7.87 (m, 2H), 8.67 (s, 2H), 10.00 (s, 1H), 13.90-0.00 (m, 1H). LCMS: R.T.=2.13 min; [M+H]+=468.0.

Workup

  1. customSolvent was removed under vacuum
  2. customthe crude product was purified by preparative HPLC on an Inertsil ODS column (19×250 mm, 5μ)
  3. customover 6 min

Sources & evidence

ORD record
ord-ae7c1ecb3f384d69aef2d31c78267f44
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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