Dimethyl Sulfoxide → HCID 178516972, compound

HRID 707449Notes

Reaction equation

HRID 707449 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[C:14]([Br:16])[N:15]=[C:10]3[N:9]([CH:17]3[CH2:19][CH2:18]3)[C:8]2=[O:20])[CH2:4]1.Cl[C:22]1[N:31]=[CH:30][C:29]2[C:24](=[CH:25][C:26]([F:32])=[CH:27][CH:28]=2)[N:23]=1.CS(C)=O.C(N(CC)C(C)C)(C)C>O.Cl.O1CCOCC1>[Br:16][C:14]1[N:15]=[C:10]2[N:9]([CH:17]3[CH2:18][CH2:19]3)[C:8](=[O:20])[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:22]4[N:31]=[CH:30][C:29]5[C:24](=[CH:25][C:26]([F:32])=[CH:27][CH:28]=5)[N:23]=4)[CH2:4]3)[C:11]2=[N:12][CH:13]=1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 210739782-Chloro-7-fluoroquinazolineHCID 178479283HCID 178479283, compound2×

Product 1

HCID 178516972HCID 178516972, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-5-bromo-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 82, 0.143 g, 0.397 mmol) and 2-chloro-7-fluoroquinazoline (0.118 g, 0.646 mmol). DMSO (2 mL) was added followed by N,N-diisopropylethylamine (0.300 mL, 1.725 mmol) and the reaction mixture was sealed under argon and heated at 100° C. overnight. The reaction was cooled room temperature and diluted with water. The precipitate was filtered to give an off-white solid. The material was dissolved in 4M HCl in dioxane and purified by reverse-phase HPLC (Gilson; Gemini-NX 10 m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA CH3CN (9:1→1:9). The fractions containing the desired product were combined and concentrated in vacuo. The residue was dissolved in MeOH and loaded onto an Si-Carbonate (Silicycle) cartridge eluting with DCM/MeOH to give 50 mg (27%) of a white crystalline solid. ESI MS 469.9, 471.8 [M+1].

Workup

  1. customA glass microwave reaction vessel
  2. customthe reaction mixture was sealed under argon
  3. temperatureThe reaction was cooled room temperature
  4. filtrationThe precipitate was filtered
  5. customto give an off-white solid
  6. custompurified by reverse-phase HPLC (Gilson; Gemini-NX 10 m C18 110A AXIA, 100×50 mm column)
  7. washeluting with 0.1% TFA-H2O
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in MeOH
  11. washeluting with DCM/MeOH

Sources & evidence

ORD record
ord-72129a68a69f4e57ba81603c9736c3b3
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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