Tetrahydrofuran → 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528553

反応式

HRID 528553 の反応式
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22](Cl)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[S:26]1[CH:30]=[C:29]([NH2:31])[N:28]=[CH:27]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O.CCCCCCC>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([NH:31][C:29]3[N:28]=[CH:27][S:26][CH:30]=3)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 14009640Thiazol-4-amineHCID 897618504-(2-Bromo-4-(Trifluoromethyl)Phenyl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride2 回

生成物 1

HCID 717116224-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide収率 21.3%

試薬・触媒・溶媒 1

HCID 21899848Ethylacetate heptane溶媒

実験手順

A round-bottom flask was charged with 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 299.84 mg, 0.657 mmol), thiazol-4-amine (79 mg, 0.788 mmol), and THF (3283 n1) to give a brown mixture. The flask was cooled in an ice-bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1379 μl, 1.379 mmol) was added dropwise over 30 s. After 30 min, the cooling bath was removed, and the mixture was allowed to warm to room temperature. The reaction mixture was quenched by the addition of aq. 1N hydrochloric acid and a small amount of brine and extracted with EtOAc (3×, emulsion). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM. The desired product was repurified again by chromatography on a 40 g silica gel column, this time with 0 to 40% EtOAc/Heptane to give 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (73.1 mg, 0.140 mmol) as a cream-colored solid. 1H NMR (400 MHz, DMSO-d6) δ=10.88 (s, 1 H), 8.88 (d, J=2.2 Hz, 1 H), 8.20 (d, J=1.5 Hz, 1 H), 7.89 (dd, J=1.6, 8.5 Hz, 1 H), 7.73 (d, J=8.4 Hz, 1 H), 7.25 (d, J=2.2 Hz, 1 H), 7.16 (dd, J=2.2, 8.6 Hz, 1 H), 6.96 (d, J=2.2 Hz, 1 H), 6.22 (d, J=8.6 Hz, 1 H), 4.36 (d, J=15.8 Hz, 2 H), 3.78-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.

後処理

  1. customto give a brown mixture
  2. temperatureThe flask was cooled in an ice-bath for 10 min
  3. customthe cooling bath was removed
  4. customThe reaction mixture was quenched by the addition of aq. 1N hydrochloric acid
  5. extractiona small amount of brine and extracted with EtOAc (3×, emulsion)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM
  10. customThe desired product was repurified again by chromatography on a 40 g silica gel column

出典と根拠

ORDレコード
ord-1ac09a2860ae4ea5a85573bbc8961a96
出典データセット
uspto-grants-2016_05
特許番号
US09346798B2

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