Hydrochloric Acid → HCID 46215813, compound

HRID 2367375Notes

Reaction equation

HRID 2367375 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([N:9]([CH3:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:3]=1.CC(OC([N:24](C(OC(C)(C)C)=O)[C:25]1[C:33]2[C:28](=[CH:29][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:32]=2)[N:27](C(OC(C)(C)C)=O)[N:26]=1)=O)(C)C.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl.Cl>CO.O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:24][C:25]1[C:33]2[C:28](=[CH:29][C:30]([C:2]3[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([N:9]([CH3:16])[C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH:3]=3)=[CH:31][CH:32]=2)[NH:27][N:26]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2387466-Chloro-2-imino-N-methyl-N-phenyl-1,2-dihydropyrimidin-4-amineHCID 58504645HCID 58504645, compound

Product 1

HCID 46215813HCID 46215813, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
150 °C

Procedure

To a 5-mL microwave vial was added 6-chloro-N4-methyl-N4-phenyl-2,4-pyrimidinediamine (61 mg, 0.260 mmol), 1,1-dimethylethyl 3-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate (218 mg, 0.390 mmol), K2CO3 (0.130 mL, 0.260 mmol), PdCl2(dppf).CH2Cl2 adduct (212 mg, 0.260 mmol) and 1,4-dioxane (3 mL). The vial was capped and stirred for 10 minutes at 150° C. in a microwave reactor. The reaction mixture was concentrated in vacuo, and the residue was dissolved in EtOAc (50 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organics were dried with Na2SO4, then filtered. The filtrate was concentrated, and dissolved in dioxane (10 mL) and CH3OH (1 mL), and HCl (0.5 mL, 2 mmol) in dioxane was added. The reaction was stirred overnight at 40° C. At this time, LCMS analysis indicated complete conversion to the desired product. The reaction mixture was concentrated, and the residue was dissolved in DMSO and purified by RP-HPLC (15-35% CH3CN in H2O; 0.1% TFA). The fractions containing the product were combined, concentrated to remove the CH3CN, basified (NaHCO3, pH paper) and extracted into EtOAc. The organic layer was dried and concentrated to afford the title compound as a yellow solid (19 mg). LC-MS (ES) m/z=332 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.46 (s, 3H), 5.38-5.52 (m, 2H), 5.94-6.15 (m, 1H), 6.25-7.00 (bs, 1H), 7.12-7.27 (m, 1H), 7.34-7.46 (m, 4H), 7.47-7.57 (m, 2H), 7.58-7.66 (m, 1H), 7.67-7.78 (m, 1H), 11.40-11.77 (m, 1H).

Workup

  1. customThe vial was capped
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in EtOAc (50 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  5. dry with materialthe combined organics were dried with Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. dissolutiondissolved in dioxane (10 mL)
  9. stirringThe reaction was stirred overnight at 40° C

Sources & evidence

ORD record
ord-0f9e6d4914e746a6b4fd945f09be92ed
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…