Potassium Phosphate, Tribasic → tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-(3-methylisoxazol-4-yl)pyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

HRID 1504875ノート

反応式

HRID 1504875 の反応式
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:11]=[C:12]([NH:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]3[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:13]=[N:14][C:15]=2[C:16]#[N:17])[CH:3]=1.[CH3:33][C:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][O:36][N:35]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:16]([C:15]1[N:14]=[CH:13][C:12]([NH:18][C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]2[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:11][C:10]=1[NH:9][C:4]1[CH:3]=[C:2]([C:38]2[C:34]([CH3:33])=[N:35][O:36][CH:37]=2)[CH:7]=[C:6]([CH3:8])[N:5]=1)#[N:17]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 772303803-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazoleHCID 86731656tert-butyl (1S,2R)-2-(5-(4-chloro-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

生成物 1

HCID 86731745tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-(3-methylisoxazol-4-yl)pyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To tert-butyl (1S,2R)-2-(5-(4-chloro-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate (PrepEx 1.7) (50 mg, 0.11 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (27 mg, 0.13 mmol), and tricyclohexylphosphine (4 mg, 0.01 mmol) in a nitrogen purged vial was added dioxane (0.6 ml) and potassium phosphate tribasic (1.25 M in water, 0.26 ml, 0.33 mmol). The reaction mixture was purged with nitrogen, and then Pd2 dba3 (5 mg, 0.005 mmol) was added. The reaction vessel was sealed and heated at 100° C. for 1 hour. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with aqueous saturated sodium bicarbonate solution (10 mL). The organics were separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (5-50% ethyl acetate/hexanes, linear gradient) to give tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-(3-methylisoxazol-4-yl)pyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate. MS ESI calc'd. for C27H34N7O3 [M+H]+ 504. found 504.

後処理

  1. customThe reaction mixture was purged with nitrogen
  2. customThe reaction vessel was sealed
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. customThe organics were separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (5-50% ethyl acetate/hexanes, linear gradient)

出典と根拠

ORDレコード
ord-8505986d6e2540ad83afe5fe9c53072a
出典データセット
uspto-grants-2015_12
特許番号
US09216173B2

反応ノート

読み込み中…