Hydrochloric Acid → HCID 56848818, compound

HRID 1470357Notes

Reaction equation

HRID 1470357 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[O:10][C:3]=12.[NH2:23][C:24]1[CH:25]=[CH:26][C:27]2[O:32][C:31]([F:34])([F:33])[C:30](=[O:35])[NH:29][C:28]=2[CH:36]=1.Cl.O1CCOCC1>>[F:34][C:31]1([F:33])[C:30](=[O:35])[NH:29][C:28]2[CH:36]=[C:24]([NH:23][C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[CH:8]=[C:9]([C:11]5[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=5)[O:10][C:3]=34)[CH:25]=[CH:26][C:27]=2[O:32]1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 22061146HCID 22061146, compoundHCID 667789647-Chloro-2-(3,4,5-trimethoxyphenyl)furo[3,2-b]pyridine

Product 1

HCID 56848818HCID 56848818, compoundYield 26%

Conditions

Temperature
150 °C

Procedure

To a 10 mL microwave vial with stirbar was added 7-chloro-2-(3,4,5-trimethoxyphenyl)furo[3,2-b]pyridine (25.00 mg; 0.08 mmol; 1.00 eq.) and 6-amino-2,2-difluoro-4H-benzo[1,4]oxazin-3-one (16.43 mg; 0.08 mmol; 1.05 eq.). The vial was sealed and flushed with N2 and the reagents were dissolved in NMP (1.00 ml). Hydrogen chloride in dioxane (0.02 ml; 4.00 M; 0.08 mmol; 1.05 eq.) was added and the reaction mixture was heated to 150° C. in a microwave reactor for 1 h. The reaction mixture was cooled to room temperature and quenched with NaOH(aq), extracted with EtOAc, dried (MgSO4) and concentrated on a rotary evaporator. The crude mixture was purified by Biotage chromatography (2-10% MeOH/CH2Cl2 15 column vol.; 10% MeOH/CH2Cl2 5 column vol.) to afford the title compound as a beige solid (10 mg, 26%). (HPLC (method F): 90%, RT: 4.69 min); 1H NMR (400 MHz, DMSO-d6) δ [ppm] 11.99 (s, 1H), 9.14 (s, 1H), 8.17 (d, J=5.5, 1H), 7.57 (s, 1H), 7.35 (d, J=8.8, 1H), 7.22 (s, 2H), 7.08-7.00 (m, 2H), 6.88 (d, J=5.5, 1H), 3.85 (s, 6H), 3.72 (s, 3H); MS (m/z) 484 [M+H]+, RT: 2.9 min.

Workup

  1. customThe vial was sealed
  2. customflushed with N2
  3. dissolutionthe reagents were dissolved in NMP (1.00 ml)
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customquenched with NaOH(aq)
  6. extractionextracted with EtOAc
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated on a rotary evaporator
  9. customThe crude mixture was purified by Biotage chromatography (2-10% MeOH/CH2Cl2 15 column vol.; 10% MeOH/CH2Cl2 5 column vol.)

Sources & evidence

ORD record
ord-351b44eb0ad54b1aad26d3d4cf7209ee
Source dataset
uspto-grants-2015_04
Patent number
US09006440B2

Reaction notes

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