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

HRID 1045983ノート

反応式

HRID 1045983 の反応式
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

参加物

9

反応物 6

HCID 10796Cesium carbonateHCID 1014122-Amino-5-fluorobenzoic acidHCID 2885605-Fluoroisatoic anhydride2 回HCID 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-methoxybenzamide2 回

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-41fa9fe684db4f9d87b54a20c6732f63
出典データセット
uspto-grants-2013_10
特許番号
US08569298B2

反応ノート

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