N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → HCID 44609039, compound
Reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:14])[N:9]([CH3:13])[CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:15][N:16]1[CH:20]=[C:19]([NH:21][C:22]2[CH:27]=[C:26](I)[C:25]([C:29]([F:32])([F:31])[F:30])=[CH:24][N:23]=2)[C:18]([CH3:33])=[N:17]1>>[CH3:15][N:16]1[CH:20]=[C:19]([NH:21][C:22]2[CH:27]=[C:26]([NH:1][C:2]3[C:7]4[C:8](=[O:14])[N:9]([CH3:13])[CH2:10][CH2:11][O:12][C:6]=4[CH:5]=[CH:4][CH:3]=3)[C:25]([C:29]([F:31])([F:30])[F:32])=[CH:24][N:23]=2)[C:18]([CH3:33])=[N:17]1Participants
Procedure
6-Amino-4-methyl-2,3-dihydro-1,4-benzoxazepin-5-one (151 mg, 0.79 mmol, see Example 3.22) and N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) were reacted using the procedure in Example 5.02. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent, followed by flash chromatography on silica gel eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness and triturated in a mixture of 30% tBuOMe in pentane to give the title compounds as a light white foam (95 mg, 54%). 1H NMR spectrum (500 MHz, CDCl3): 2.15 (s, 3H), 3.21 (s, 3H), 3.50 (t, 2H), 3.81 (s, 3H), 4.35 (t, 2H), 6.19 (s, 1H), 6.30 (s, 1H), 6.70 (dd, 1H), 7.19 (dd, 1H), 7.23 (dd, 1H), 7.38 (s, 1H), 8.20 (s, 1H), 9.21 (s, 1H); Mass spectrum: ESI+ MH+ 447.
Workup
- customThe reaction mixture was purified by preparative HPLC
- customThe solvent was evaporated to dryness
- customtriturated in a mixture of 30% tBuOMe in pentane
Sources & evidence
- ORD record
- ord-5c308a8a511b474c87c71efaf8b36c71
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08569298B2
Reaction notes
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