H-GLY-NHME HCL

A solution of tert-butyl N- [(methylcarbamoyl)methyl]carbamate (300 mg, 1.59 mmol, 1.00 equiv) in DCM (5 mL) was added hydrochloric acid (1.2 mL) and stirred for 4 h at room temperature. The resulting mixture was concentrated under vacuum to afford the corresponding 2-amino-N-methylacetamide hydrochloride (185 mg) as a colorless oil. MS: m/z 89 (M+H)To a solution of phenyl (3, 5-difluoro-4-{[3-(trifluoromethyl)-1 -{[2-(trimethylsilyl)ethoxy]methyl}- 1 H-pyrrolo[2, 3-b]pyridin-4-yl]oxy}phenyl)carbamate (150 mg, 259 muetaetaomicronIota, intermediate 1 ) in DMF (1 .3 mL) was added N-methylglycinamide hydrochloride (1 :1 ) (32.2 mg, 259 muetaiotaomicronIota) and N, N- diisopropylethylamine (45 muIota_, 260 muetaetaomicronIota) and this mixture was stirred at 50C for 12 hours. After cooling to room temperature ethyl acetate and water was added. After separation of the organic phase the aqueous phase was extracted two times with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The resulting residue was purified via a Biotage chromatography system (1 Og snap KP-Sil column, hexane / 0 - 100% ethyl acetate, then ethyl acetate / 0 - 100% methanol) to obtain 146 mg (95 % purity, 93 % yield) of the desired title compound. 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.10 - -0.05 (m, 9H), 0.80 - 0.86 (m, 2H), 2.61 (d, 3H), 3.55 - 3.60 (m, 2H), 3.71 (d, 2H), 5.68 (s, 2H), 6.56 - 6.61 (m, 2H), 7.34 - 7.41 (m, 2H), 7.91 (q, 1 H), 8.29 (d, 1 H), 8.36 (s, 1 H), 9.34 (s, 1 H).General procedure: GlyNH2HCl (for 3a, 3l, 0.464 g, 4.20 mmol) or GlyNHCH3HCl (for 3m, 0.523 g, 4.20 mmol) were suspended in DMF (4 mL) withtriethylamine (0.585 mL, 4.20 mmol) under vigorous magnetic stirring while heating at 70 C. Thesuitable bromide 2a (0.143 g, 0.60 mmol) or 2c (0.179 g, 0.60 mmol), previously dissolved in DMF(2 mL), was added portion-wise within 3.5 h (0.250 mL every 30 min). The mixture was stirred at 70 C for an additional 4 h. After cooling at room temperature, brine (50 mL) was added, and the mixturewas extracted with ethyl acetate (3 30 mL). The organic layers were collected, washed with brine(3 x 20 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude mixtures werefurther purified as indicated below. N2-[(2-oxo-2H-Chromen-3-yl)methyl]glycinamide (3a): Purification through flash chromatography(gradient eluent: methanol in chloroform 0%5%). Yield: 62%.

Molecular Weight:124.57
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:124.0403406
Monoisotopic Mass:124.0403406
Topological Polar Surface Area:55.1
Heavy Atom Count:7
Complexity:52.8
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes