1,1'-Carbonyldiimidazole → HCID 11525808, compound

HRID 494693Notes

Reaction equation

HRID 494693 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]([C:19](O)=[O:20])=[CH:17][C:12]3[C:13]([CH3:16])=[N:14][O:15][C:11]=3[C:10]=2[F:22])=[C:4]([Cl:23])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:36][S:37]([NH2:40])(=[O:39])=[O:38].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]([C:19]([NH:40][S:37]([CH3:36])(=[O:39])=[O:38])=[O:20])=[CH:17][C:12]3[C:13]([CH3:16])=[N:14][O:15][C:11]=3[C:10]=2[F:22])=[C:4]([Cl:23])[CH:3]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11567514HCID 11567514, compound

Product 1

HCID 11525808HCID 11525808, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methylbenzo[d]isoxazole-5-carboxylic acid (9a) (41 mg, 0.102 mmol) and carbonyldiimidazole (23 mg, 0.140 mmol) in THF (1 mL) was stirred at 50° C. in a sealed tube reactor. The reaction mixture was cooled to room temperature and methanesulfonamide (17 mg, 0.179 mmol) was added followed by DBU (0.025 mL, 0.164 mmol). After stirring at 50° C. for 1 hour, the reaction mixture was cooled to room temperature, and diluted with EtOAc. The organic layer was washed with water, 1 N HCl, and brine. The organic layer was dried (MgSO4) and concentrated. Purification by flash column chromatography using the Biotage system (7% MeOH in CH2Cl2) provided 34 mg (65% yield) of the desired product (13a). MS APCI (−) m/z 474, 476 (M+, Br, Cl pattern) detected. 1H NMR (400 MHz, CD3OD) δ 8.27 (s, 1H), 7.53 (s, 1H), 7.27 (d, 1H), 6.73 (t, 1H), 3.11 (s, 3H), 2.55 (s, 3H): 19F NMR (376 MHz, CD3OD)−141.84 (s, 1F).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringAfter stirring at 50° C. for 1 hour
  3. temperaturethe reaction mixture was cooled to room temperature
  4. washThe organic layer was washed with water, 1 N HCl, and brine
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-79b3febbe76848abad91ec7f5792e576
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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