Water → HCID 53374070, compound

HRID 869684Notes

Reaction equation

HRID 869684 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:5]2[N:15]=[C:16]([C:18]3[C:27]([CH3:28])=[N:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH:17]=[C:4]2[N:3]=1.Cl.[F:30][C@@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1.C(N(C(C)C)CC)(C)C.O>CN1CCCC1=O>[F:30][C@@H:31]1[CH2:35][CH2:34][N:33]([C:2]2[CH:7]=[C:6]([NH:8][CH:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[N:5]3[N:15]=[C:16]([C:18]4[C:27]([CH3:28])=[N:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[CH:17]=[C:4]3[N:3]=2)[CH2:32]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 86674506HCID 86674506, compound

Product 1

HCID 53374070HCID 53374070, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 5-chloro-2-(3-methylquinoxalin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (Example 1.001 (g)) (4.26 g, 10.8 mmol), (R)-3-fluoropyrrolidine hydrochloride (13.7 g, 108 mmol), and diisopropylethylamine (20.7 g, 160 mmol) in N-methyl-2-pyrrolidinone (108 mL) was heated 80° C. for 3 days. After being cooled to ambient temperature, the reaction mixture was poured into water. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over sodium sulfate, filtrate, and concentrated in vacuo. The residue was purified by silica gel column chromatography (silica gel 800 g, hexane:ethyl acetate=1:1 to ethyl acetate) to give 5-[(3R)-3-fluoropyrrolidin-1-yl]-2-(3-methylquinoxalin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine. MS (APCI): m/z 448 (M+H).

Workup

  1. temperatureAfter being cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with water and saturated brine
  4. dry with materialdried over sodium sulfate, filtrate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (silica gel 800 g, hexane:ethyl acetate=1:1 to ethyl acetate)

Sources & evidence

ORD record
ord-3015e76b1e594d21aa3ccf851ccc86c9
Source dataset
uspto-grants-2015_03
Patent number
US08969376B2

Reaction notes

Loading…