Hydrochloric Acid → HCID 67349795, compound

To 1H-indole-6-carboxylic acid, 7-chloro-3-cyclohexyl-2-phenyl-, methyl ester (62 mg, 0.169 mmol) under N2 at r.t. in a microwave reaction tube was added a solution of methyl (2R)-glycidate (69 mg, 0.676 mmol) in DMSO (1 ml) and NaH (27 mg, 0.675 mmol, 60% in oil), and the reaction mixture stirred at r.t. for 1 hr 25 min. The reaction mixture was then placed under microwave irradiation in an Emrys Optimizer (Personal Chemistry) at 200° C. and with the absorption level set to high for 30 min. The mixture was acidified with hydrochloric acid (1N), diluted with water. The brown precipitates were filtered, washed with water twice and then dried. The material was then dissolved in a mixture of benzene/MeOH (1 ml/1 ml), and added with TMSCHN2 (0.34 ml, 0.68 mmol, 2M in hexane). The reaction was then stirred at r.t. for 2 hr 20 min., quenched with AcOH and the volatiles were evaporated. The residue was purified by Biotage flash chromatography (gradient elution, 0 to 50% EtOAc/Hexane) to gave the dimethyl ester (1,4-oxazino[2,3,4-hi]indole-2,9-dicarboxylic acid, 6-cyclohexyl-2,3-dihydro-5-phenyl-, dimethyl ester). The stereochemical integrity at the α-hydroxyl carbon (C2) was not determined. 1H NMR (500 MHz): (CD3OD) δ 7.59-7.56 (overlapping m, 3H), 7.53-7.51 (m, 1H), 7.43 (d, J=8.5, 2H), 7.37 (d, J=8.5, 1H), 5.41 (t, J=3.8, 1H), 4.47 (dd, J=3.8, 12.8, 1H), 4.18 (dd, J=3.8, 12.8, 1H), 3.92 (s, 3H), 3.74 (s, 3H), 2.74 (m, 1H), 1.98-1.75 (b overlapping m, 7H), 1.40-1.31 (b m, 3H); Analytical HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Flow Rate=5 ml/min, Column: Xterra MS C18 S7 3.0×50 mm; LC/MS: (ES+) m/z (M+H)+=434.15, HPLC Rt=2.000 min.

1. customThe reaction mixture was then placed under microwave irradiation in an Emrys Optimizer (Personal Chemistry) at 200° C. and with the absorption level
2. customhigh for 30 min
3. customThe brown precipitates
4. filtrationwere filtered
5. washwashed with water twice
6. customdried
7. dissolutionThe material was then dissolved in a mixture of benzene/MeOH (1 ml/1 ml)
8. stirringThe reaction was then stirred at r.t. for 2 hr 20 min.
9. customquenched with AcOH
10. customthe volatiles were evaporated
11. customThe residue was purified by Biotage flash chromatography (gradient elution, 0 to 50% EtOAc/Hexane)

ORD record

ord-22a0c4837de44e6693e3ebf9c639c2da

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998951B2