2-Bromoanisole → HCID 89761777, compound

HRID 528593Notes

Reaction equation

HRID 528593 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[S:10]1[CH:14]=[CH:13][N:12]=[C:11]1[NH:15][S:16]([C:19]1[CH:20]=[CH:21][C:22]2[NH:27][CH2:26][CH2:25][O:24][C:23]=2[CH:28]=1)(=[O:18])=[O:17].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:9][O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:27]1[CH2:26][CH2:25][O:24][C:23]2[CH:28]=[C:19]([S:16]([NH:15][C:11]3[S:10][CH:14]=[CH:13][N:12]=3)(=[O:18])=[O:17])[CH:20]=[CH:21][C:22]1=2

Participants

7

Reactant 4

HCID 113582-BromoanisoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 89761796HCID 89761796, compound

Product 1

HCID 89761777HCID 89761777, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

A microwave vial was charged with 1-bromo-2-methoxybenzene (0.056 ml, 0.454 mmol), N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.090 g, 0.303 mmol), Xantphos (0.035 g, 0.061 mmol), Pd2(dba)3 (0.028 g, 0.030 mmol) and sodium tert-butoxide (0.087 g, 0.908 mmol). The mixture was diluted with toluene (3.03 ml), and purged with nitrogen, and stirred at 130° C. in the microwave for 15 minutes, until clean conversion to the desired product. The reaction was filtered over a plug of Celite, washing well with DCM. The filtrate was concentrated in vacuo and further purified using a 2-g SCX column (product eluted with methanol wash). The crude material was concentrated and absorbed directly onto a 12-g RediSep Gold column and purified by silica-gel chromatography, eluting with a gradient of 0% to 100% ethyl acetate in heptanes to provide 4-(2-methoxyphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.59-3.65 (m, 2 H) 3.74 (s, 3 H) 4.29 (t, J=4.35 Hz, 2 H) 6.16 (d, J=8.41 Hz, 1 H) 6.76 (d, J=4.60 Hz, 1 H) 7.00-7.04 (m, 1 H) 7.04-7.11 (m, 2H) 7.17 (dd, J=8.31, 1.27 Hz, 1 H) 7.21 (d, J=4.60 Hz, 1 H) 7.28 (dd, J=7.78, 1.61 Hz, 1 H) 7.31-7.37 (m, 1 H) 12.52 (br. s., 1 H). m/z (ESI) 404.0 (M+H)+.

Workup

  1. custompurged with nitrogen
  2. filtrationThe reaction was filtered over a plug of Celite
  3. washwashing well with DCM
  4. concentrationThe filtrate was concentrated in vacuo
  5. customfurther purified
  6. washa 2-g SCX column (product eluted with methanol wash)
  7. concentrationThe crude material was concentrated
  8. customabsorbed directly onto a 12-g RediSep Gold column
  9. custompurified by silica-gel chromatography
  10. washeluting with a gradient of 0% to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-e545a75c7afe484ab460424ecb6e3929
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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