Hydrochloric Acid → (S)-1-(5-(7H-purin-2-yloxy)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone

HRID 1051666Notes

Reaction equation

HRID 1051666 reaction equation
[CH:1]1([N:4]2[CH:8]=[C:7]([C:9]3[C:10]([O:23][C:24]4[N:32]=[C:31]5[C:27]([N:28](C6CCCCO6)[CH:29]=[N:30]5)=[CH:26][N:25]=4)=[C:11]4[C:16](=[CH:17][CH:18]=3)[N:15]([C:19](=[O:21])[CH3:20])[C@@H:14]([CH3:22])[CH2:13][CH2:12]4)[CH:6]=[N:5]2)[CH2:3][CH2:2]1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CO>[N:25]1[CH:26]=[C:27]2[C:31]([N:30]=[CH:29][NH:28]2)=[N:32][C:24]=1[O:23][C:10]1[C:9]([C:7]2[CH:6]=[N:5][N:4]([CH:1]3[CH2:3][CH2:2]3)[CH:8]=2)=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][CH2:13][C@H:14]([CH3:22])[N:15]2[C:19](=[O:21])[CH3:20]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 1180764371-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Product 1

HCID 118075623(S)-1-(5-(7H-purin-2-yloxy)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

A 100-mL, round-bottom flask was charged with 1-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.150 g, 0.29 mmol), HCl (6 M aqueous solution, 3 mL) and methanol (20 mL). The resulting solution stirred overnight at 40° C. After cooling to room temperature, the pH of the reaction mixture was adjusted to 7-8 with saturated aqueous sodium carbonate solution. The resulting mixture was concentrated to remove the methanol and ethyl acetate was added. The aqueous layer was separated and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 19×150 mm; mobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (37% acetonitrile up to 58% in 10 min, flow rate: 20 mL/min); Detector, UV 220&254 nm. This afforded (S)-1-(5-(7H-purin-2-yloxy)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.030 g, 24%) as a yellow solid. 1H NMR (300 MHz, CD3OD) δ ppm 0.86-1.00 (m, 4H), 1.16 (d, J=6.30 Hz, 3H), 1.21-1.49 (m, 1H), 2.18-2.47 (m, 5H), 2.63-2.72 (m, 1H), 3.52-3.59 (m, 1H), 4.72-4.80 (m, 1H), 7.19-7.30 (m, 1H), 7.56 (d, J=8.40 Hz, 1H), 7.60 (s, 1H), 7.99 (s, 1H), 8.41 (s, 1H), 8.79 (s, 1H). MS (ESI, pos. ion) m/z 430 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationThe resulting mixture was concentrated
  3. customto remove the methanol and ethyl acetate
  4. additionwas added
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate (3×20 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by preparative-HPLC with the following conditions (Waters I)
  11. waitmobile phase, water (0.05% ammonium bicarbonate) and acetonitrile (37% acetonitrile up to 58% in 10 min

Sources & evidence

ORD record
ord-3988a675ea6d4b5bb2b9621331e8e7df
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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