Trifluoroacetic acid → HCID 86679774, compound

HRID 77483Notes

Reaction equation

HRID 77483 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[N:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26](C3CCCCO3)[N:25]=[CH:24]4)=[CH:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([F:11])[F:10].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:26]1[C:27]2[C:23](=[CH:22][C:21]([CH2:20][CH2:19][C:16]3[CH:17]=[N:18][C:13]([NH:12][C:4]4[CH:5]=[CH:6][C:7]([O:8][CH:9]([F:11])[F:10])=[C:2]([Cl:1])[CH:3]=4)=[N:14][CH:15]=3)=[CH:29][CH:28]=2)[CH:24]=[N:25]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86679772HCID 86679772, compound

Product 1

HCID 86679774HCID 86679774, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N-(3-chloro-4-(difluoromethoxy)phenyl)-5-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)ethyl)pyrimidin-2-amine (0.075 g, 0.150 mmol) in DCM (5 mL) was added TFA (0.116 mL, 1.500 mmol) and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated and the crude product purified by preparative HPLC on a Symmetry C18 column (19×300 mm, 7 μm) using 0-100% mobile phase B (ACN) in mobile phase A (10 mM ammonium acetate) to give 5-(2-(1H-indazol-5-yl)ethyl)-N-(3-chloro-4-(difluoromethoxy)phenyl)pyrimidin-2-amine as an off white solid (0.012 g, 19% yield). 1HNMR 400 MHz, DMSO-d6: δ 2.85 (t, J=15.60 Hz, 2H), 2.99 (t, J=14.80 Hz, 2H), 6.95-7.31 (m, 3H), 7.46 (d, J=8.40 Hz, 1H), 7.54 (s, 1H), 7.65-7.68 (m, 1H), 7.98 (s, 1H), 8.08 (d, J=2.80 Hz, 1H), 8.36 (s, 2H), 9.76 (s, 1H), 12.95 (s, 1H). LCMS (ES-API), RT: 2.15 min, m/z 414 (M−H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe crude product purified by preparative HPLC on a Symmetry C18 column (19×300 mm, 7 μm)

Sources & evidence

ORD record
ord-efe815d492644c4598f3250239cb76fa
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

Loading…