Toluene → 5,6-Disubstituted anthranilic acid sulfonamide, 9e

HRID 1725928

반응식

HRID 1725928 반응식
Br[C:2]1[C:3]([CH3:29])=[C:4]([C:15]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)(=[O:21])=[O:20])=[CH:16][CH:17]=1)[C:5]([O:7]CC1C=CC=CC=1)=[O:6].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:38](B(O)O)[CH2:39][CH2:40][CH3:41].C1(C)C=CC=CC=1>C(OCC)(=O)C.C1(P([Pd](Cl)(Cl)P(C2CCCCC2)(C2CCCCC2)C2CCCCC2)(C2CCCCC2)C2CCCCC2)CCCCC1.O>[CH2:38]([C:2]1[C:3]([CH3:29])=[C:4]([C:15]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)(=[O:20])=[O:21])=[CH:16][CH:17]=1)[C:5]([OH:7])=[O:6])[CH2:39][CH2:40][CH3:41]

참가 물질

8

반응물 4

HCID 1140TolueneHCID 20479Butylboronic AcidHCID 62657Potassium Phosphate, TribasicHCID 68864112Benzyl 3-bromo-6-{[(4-fluorophenyl)sulfonyl]amino}-2-methylbenzoate

생성물 1

HCID 236477655,6-Disubstituted anthranilic acid sulfonamide, 9e

시약·촉매·용매 3

HCID 178479803HCID 178479803, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A mixture of Example 225A (123 mg, 0.26 mmol), potassium phosphate (192 mg, 0.9 mmol), butylboronic acid (34 mg, 0.33 mmol), bis(tricyclohexylphosphino)palladium dichloride (19 mg, 0.03 mmol), toluene (4 mL), and water (0.2 mL) was purged with argon and shaken at 100° C. for 36 hours in a sealed container. The mixture was diluted with ethyl acetate (10 mL), washed with water (2×10 mL) and brine, dried (Na2SO4), filtered, concentrated and passed through a silica gel cartridge (20 g) with 15% ethyl acetate/hexanes. The isolated solid was substituted for Example 108C in Example 108D and purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/0.1% aqueous TFA over 8 minutes (10 minute run time) at a flow rate of 40 mL/min to provide the desired-product. MS (ESI(+)) m/e 383 (M+NH4)+; (ESI(−)) m/e 364 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 13.09 (br s, 1H), 9.74 (br s, 1H), 7.78 (m, 2H), 7.39 (m, 2H), 7.08 (d, 1H), 6.71 (d, 1H), 2.55 (q, 2H), 2.18 (s, 3H), 1.44 (m, 2H), 1.32 (m, 2H), 0.91 (t, 3H).

후처리

  1. washwashed with water (2×10 mL) and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)
  6. customover 8 minutes
  7. custom(10 minute run time)
  8. customto provide the desired-product

출처 및 근거

ORD 기록
ord-ae1c384e886e4e6883cc58838382736c
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07491718B2

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