Potassium Carbonate → 4-((1R,2S)-2-aminocyclohexylamino)-5-fluoro-2-(3-methylisothiazol-5-ylamino)benzamide

HRID 2201067

反応式

HRID 2201067 の反応式
Br[C:2]1[C:3]([C:24]#[N:25])=[CH:4][C:5]([F:23])=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15]C(=O)OC(C)(C)C)[CH:7]=1.Cl.[NH2:27][C:28]1[S:32][N:31]=[C:30]([CH3:33])[CH:29]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=[O:81].[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:6]1[C:5]([F:23])=[CH:4][C:3]([C:24]([NH2:25])=[O:81])=[C:2]([NH:27][C:28]2[S:32][N:31]=[C:30]([CH3:33])[CH:29]=2)[CH:7]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 69283992tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate

生成物 1

HCID 692839864-((1R,2S)-2-aminocyclohexylamino)-5-fluoro-2-(3-methylisothiazol-5-ylamino)benzamide収率 74.2%

試薬・触媒・溶媒 2

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

実験手順

A mixture of tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate (220 mg, 0.534 mmol), 5-amino-3-methylisothiazole hydrochloride (97 mg, 0.644 mmol), BINAP (50 mg, 0.080 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (250 mg, 1.81 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 120 C for 18 h. After the mixture was filtered, the filtrate was concentrated in vacuo. To a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added. After being stirred at room temperature for 3 h, water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was dissolved in TFA (5 mL). After 30 min of standing, TFA was removed in vacuo. The residue was purified by HPLC to give the titled compound (144 mg). MS 364.4 (M+H); UV 204.7, 292.8 nm

後処理

  1. customwas degassed with Ar
  2. filtrationAfter the mixture was filtered
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionTo a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added
  5. stirringAfter being stirred at room temperature for 3 h
  6. additionwater and EtOAc were added
  7. customThe organic phase was separated
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in TFA (5 mL)
  11. waitAfter 30 min of standing
  12. customTFA was removed in vacuo
  13. customThe residue was purified by HPLC

出典と根拠

ORDレコード
ord-76780ca4b20b4680a92aadb282d56db2
出典データセット
uspto-grants-2016_06
特許番号
US09359375B2

関連ノート

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