Potassium Carbonate → HCID 86687535, compound

HRID 1473483Notes

Reaction equation

HRID 1473483 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[C:35]([O:42][CH3:43])[CH:34]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:31][O:30][C:23]1[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=1[CH2:21][N:15]([C:16]1[S:17][CH:18]=[CH:19][N:20]=1)[S:12]([C:8]1[CH:7]=[C:6]2[C:11]([C:2]([C:36]3[CH:37]=[CH:38][C:33]([F:32])=[CH:34][C:35]=3[O:42][CH3:43])=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1)(=[O:14])=[O:13]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 86687456HCID 86687456, compound

Product 1

HCID 86687535HCID 86687535, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A microwave vial was charged with 4-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (Intermediate KKKK; 0.040 g, 0.084 mmol), (4-fluoro-2-methoxyphenyl)boronic acid (0.021 g, 0.126 mmol), tetrakis(triphenylphosphine)palladium(0) (9.69 mg, 8.39 μmol), and potassium carbonate (0.058 g, 0.419 mmol). Dioxane (0.419 mL) and water (0.140 mL) were added, the vial was flushed with argon and sealed, and microwaved at 100° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (12 g silica gel column, gradient elution 0 to 100% EtOAc:Heptane) to afford N-(2,4-dimethoxybenzyl)-4-(4-fluoro-2-methoxyphenyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred overnight at room temperature. The reaction was concentrated and purified via column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM) to afford 4-(4-fluoro-2-methoxyphenyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=13.01 (br. s., 1H), 9.45 (s, 1H), 8.38 (br. s., 1H), 8.06-7.76 (m, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.31 (d, J=4.1 Hz, 1H), 7.21 (d, J=11.2 Hz, 1H), 7.01 (t, J=7.1 Hz, 1H), 6.90 (d, J=4.3 Hz, 1H), 3.70 (br. s., 3H). m/z (ESI) 417.2 (M+H)+.

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. custommicrowaved at 100° C. for 30 minutes
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography (12 g silica gel column, gradient elution 0 to 100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-ee4fa1f6adc249e8a7a31812a69c1440
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…