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 1438604노트

반응식

HRID 1438604 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

반응 조건

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-b23cc917bf0940cfbfe64d4890d66c4b
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07622583B2

반응 노트

불러오는 중…