Sodium hydride → HCID 59694486, compound

Participants

Reaction Steps

(S)-2-(1-Hydroxy-3-(1H-indol-3-yl)propan-2-yl)isoindoline-1,3-dione (150 mg, 0.47 mmol) and 60% sodium hydride in mineral oil (37.6 mg, 0.94 mmol) was mixed in 2 ml N-methylpyrrolidinone. After stirring for ten minutes, compound 1b suspended in 2 ml N-methylpyrrolidinone was added and the reaction mixture was stirred at 20° C. for an hour. The reaction mixture was partitioned between ethylacetate and saturated aqueous ammonium chloride. The ethylacetate phase was washed with more saturated aqueous ammonium chloride and dried over anhydrous sodium sulfate. After removing the ethylacetate, the remaining residue was subjected to a silica gel column chromatography separation to yield the intermediate 2-((S)-3-(1H-indol-3-yl)-1-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yloxy)propan-2-yl)isoindoline-1,3-dione (3a). Compound 3a was dissolved in 4 ml ethyl alcohol, 0.5 ml water and 0.5 ml hydrazine monohydrate in a microwave heating tube. The tube was heated at 100° C. under microwave for five minutes. After removing all the solvent, the residue was subjected to a C18 reverse phase HPLC separation to yield (2S)-1-(1H-indol-3-yl)-3-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yloxy)propan-2-amine (3) (2.4 mg) as a TFA salt. 1H NMR (400 MHz, Methanol-d4): δ 3.08 (m, 1H), 3.12 (m, 1H), 3.58 (m, 2H), 3.74 (m, 1H), 7.33 (t, J=7.2 Hz, 1H), 7.41 (t, J=7.2 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 8.32 (m, 2H), 8.46 (d, J=8.8 Hz, 1H), 8.53 (m, 2H), 8.72 (s, 1H), 9.60 (s, 1H); MS (API-ES) m/z (%): 402 (95%, M++1), 424 (100%, M+Na+); HRMS (ESI): calculated for C22H19N5OS [M+1]: 402.1388; found: 402.1394.

Provenance & Evidence