[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.CN(C(SC1[N+]([O-])=CC=CC=1)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:49][C:50]1[CH:51]=[C:52]2[C:56](=[CH:57][CH:58]=1)[N:55]([NH2:59])[CH2:54][C:53]2([CH3:61])[CH3:60]>CN(C=O)C.O.CCOC(C)=O>[F:49][C:50]1[CH:51]=[C:52]2[C:56](=[CH:57][CH:58]=1)[N:55]([NH:59][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=1)=[O:17])[CH2:54][C:53]2([CH3:61])[CH3:60]A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (348 mg, 1.5 mmol), HOTT (618 mg, 1.66 mmol), and DIPEA (700 μL, 4.01 mmol) in DMF (10 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-3,3-dimethyl-2,3-dihydro-indol-1-ylamine (239 mg, 1.33 mmol) is added. The resulting mixture is stirred at 80° C. overnight. The mixture is cooled and portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 15% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-amide (416 mg, 80%) as a solid. MS: 395 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 10.43 (s, 1H), 8.99 (s, 1H), 8.28 (d, 1H), 8.15-8.11 (m, 1H), 7.66-7.58 (m, 1H), 7.46-7.39 (m, 1H), 7.06 (dd, 1H), 6.95-6.88 (m, 1H), 6.75-6.71 (m, 1H), 3.51 (s, 2H), 2.68 (s, 3H), 1.33 (s, 6H).
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