Cesium carbonate → 2-[[2-Chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-n-methoxy-benzamide

HRID 1045983

반응식

HRID 1045983 반응식
NC1C=CC(F)=CC=1C(O)=O.FC1C=CC2NC(=O)OC(=O)C=2C=1.[NH2:25][C:26]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:27]=1[C:28]([NH:30][O:31][CH3:32])=[O:29].[Cl:38][C:39]1[CH:44]=[C:43](I)[C:42]([C:46]([F:49])([F:48])[F:47])=[CH:41][N:40]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:38][C:39]1[CH:44]=[C:43]([NH:25][C:26]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:27]=2[C:28]([NH:30][O:31][CH3:32])=[O:29])[C:42]([C:46]([F:47])([F:48])[F:49])=[CH:41][N:40]=1

참가 물질

9

반응물 6

HCID 10796Cesium carbonateHCID 1014122-Amino-5-fluorobenzoic acidHCID 2885605-Fluoroisatoic anhydride2회HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27737912-Chloro-4-iodo-5-(trifluoromethyl)pyridineHCID 569516602-amino-5-fluoro-N-methoxybenzamide2회

생성물 1

HCID 872598082-[[2-Chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-n-methoxy-benzamide수율 40.5%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

Using the procedure in example 15.01, 2-amino-5-fluorobenzoic acid (1.5 g, 9.67 mmol) was converted into 6-fluoro-1H-3,1-benzoxazine-2,4-dione (1.2 g, 68.5%) as an pale yellow solid; and 6-fluoro-1H-3,1-benzoxazine-2,4-dione (1.05 g, 5.80 mmol) converted into 2-amino-5-fluoro-N-methoxybenzamide (0.344 g, 32.2%) as a yellow pale solid after purification by 2 flash chromatographies on silica gel (eluting with 0 to 50% EtOAc in DCM; eluting with 20% EtOAc in DCM). NMR Spectrum: (DMSOd6) 3.68 (s, 3H), 6.19 (bs, 2H), 6.72 (dd, 1H), 7.07 (ddd, 1H), 7.15 (dd, 1H), 11.48 (bs, 1H) 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (0.502 g, 1.63 mmol), 2-amino-5-fluoro-N-methoxybenzamide (0.344 g, 1.68 mmol), palladium(II) acetate (0.029 g, 0.13 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.151 g, 0.26 mmol) and cesium carbonate (0.638 g, 1.96 mmol) were weighed out in a microwave vial and sealed. Dioxane (10.3 ml) was added and argon bubbled through the reaction mixture followed by stirring at 90° C. for 5 hours. The reaction mixture was allowed to cool to room temperature, silica gel was added and the mixture was concentrated to afford the crude, which was purified by flash chromatography on silica gel eluting with 20 to 50% EtOAc. The solvent was evaporated to dryness to afford 2-[[2-chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-N-methoxy-benzamide (0.240 g, 40%) as an yellow oil which crystallised on standing. NMR Spectrum: (DMSOd6) 3.62 (s, 3H), 6.85 (s, 1H), 7.43-7.51 (m, 2H), 7.60 (dd, 1H), 7.44 (s, 1H), 9.37 (bs, 1H), 11.88 (bs, 1H); Mass spectrum: MH+ 364

후처리

  1. customafter purification by 2 flash chromatographies on silica gel (eluting with 0 to 50% EtOAc in DCM; eluting with 20% EtOAc in DCM)
  2. customsealed
  3. customargon bubbled through the reaction mixture
  4. temperatureto cool to room temperature
  5. additionsilica gel was added
  6. concentrationthe mixture was concentrated
  7. customto afford the crude, which
  8. customwas purified by flash chromatography on silica gel eluting with 20 to 50% EtOAc
  9. customThe solvent was evaporated to dryness

출처 및 근거

ORD 기록
ord-41fa9fe684db4f9d87b54a20c6732f63
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569298B2

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