Hydrochloric Acid → 1-(3-Bromophenyl)-1-(3-fluoropyridin-4-yl)-1H-isoindol-3-amine

HRID 2264734노트

반응식

HRID 2264734 반응식
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[Br:20][C:21]1[CH:22]=[C:23]([C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]#[N:42])=[N:28]S(C(C)(C)C)=O)[CH:24]=[CH:25][CH:26]=1.Cl>O1CCCC1.O>[Br:20][C:21]1[CH:22]=[C:23]([C:27]2([C:19]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[F:13])[C:35]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:41]([NH2:42])=[N:28]2)[CH:24]=[CH:25][CH:26]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 677943-FluoropyridineHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

생성물 1

HCID 595962811-(3-Bromophenyl)-1-(3-fluoropyridin-4-yl)-1H-isoindol-3-amine수율 64%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

실험 절차

To a −78° C. solution of diisopropylamine (0.77 mL, 5.50 mmol) in tetrahydrofuran (10 mL) was n-butyllithium (2.5 M in hexane, 2.20 mL, 5.50 mmol) added, the mixture was stirred 0.5 h and then a solution of 3-fluoropyridine (0.47 mL, 5.50 mmol) in tetrahydrofuran (2 mL) was added and after another 0.5 h N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.95 g, 5.0 mmol) in tetrahydrofuran (5 mL) was added. After 1.5 h at −78° C. water was added, the mixture was extracted with ethyl acetate, the organic phase was dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (40 mL) and treated with hydrochloric acid (2 M in diethylether, 5 mL, 10.0 mmol) over night. After evaporation, the residue was partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and evaporated. Purification of the residue by column chromatography using a stepwise gradient of methanol in chloroform (0-10%) as the eluent gave the title compound (1.22 g, 64%). 1H NMR (CDCl3) δ 8.43 (d, J=2.78 Hz, 1 H), 8.35 (d, J=5.05 Hz, 1 H), 7.76 (d, J=8.08 Hz, 1 H), 7.60-7.50 (m, 3 H), 7.45-7.37 (m, 2 H), 7.37-7.33 (m, 1 H), 7.20-7.13 (m, 2 H), 5.37 (br s, 2 H); MS (AP) m/z 382, 384 [M+1]+.

후처리

  1. customTo a −78° C.
  2. additionadded
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialthe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methanol (40 mL)
  8. customAfter evaporation
  9. customthe residue was partitioned between aqueous saturated sodium bicarbonate and chloroform
  10. dry with materialthe organic phase was dried over magnesium sulfate
  11. customevaporated
  12. customPurification of the residue by column chromatography

출처 및 근거

ORD 기록
ord-bcf62904e0d640428114bec23bfc6c3c
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855213B2

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