N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamide → 8-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester

HRID 1898172노트

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HRID 1898172 반응식
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[C:32]([O:36][C:37]([N:39]1[C:44]2[CH:45]=[CH:46][CH:47]=[C:48]([CH:49]=[O:50])[C:43]=2[O:42][CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]>C1COCC1>[C:32]([O:36][C:37]([N:39]1[C:44]2[CH:45]=[CH:46][CH:47]=[C:48]([CH:49]([C:2]3[C:7]([N:8]([S:9]([C:12]4[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=4)(=[O:11])=[O:10])[CH2:23][O:24][CH3:25])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=3)[OH:50])[C:43]=2[O:42][CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

참가 물질

5

반응물 3

HCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 57942605Tert-butyl 8-formyl-2,3-dihydro-4H-benzo[B][1,4]oxazine-4-carboxylateHCID 178418918HCID 178418918, 화합물

생성물 1

HCID 666489408-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester수율 56.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (2.92 g, 6.18 mmol) in THF (12 mL) under nitrogen atmosphere at −20° C. was added isopropylmagnesium chloride (2 M solution in THF, 6.5 mL, 13.0 mmol) via dropwise addition. The mixture was then stirred for 1 hour at 0° C. followed by the addition of a solution of 8-formyl-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (273.5 mg, 1.54 mmol) in THF (2 mL) at −20° C. The mixture was stirred at room temperature overnight, quenched with saturated aqueous NH4Cl solution (5 mL), and extracted with EtOAc (2×200 mL). The combined organic extracts were washed with saturated aqueous NH4Cl solution (40 mL) and brine (40 mL), dried (Na2SO4), and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (10% EtOAc-hexanes to 90% EtOAc-hexanes) to obtain 8-({5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (590.2 mg) as yellow syrup. MS m/z: 678.0 (M+H)+.

후처리

  1. additionvia dropwise addition
  2. stirringThe mixture was stirred at room temperature overnight
  3. customquenched with saturated aqueous NH4Cl solution (5 mL)
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined organic extracts were washed with saturated aqueous NH4Cl solution (40 mL) and brine (40 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by flash column chromatography on silica gel (10% EtOAc-hexanes to 90% EtOAc-hexanes)

출처 및 근거

ORD 기록
ord-b6b728ce8be14e3395cf347b798160d8
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08519135B2

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