Potassium Phosphate, Tribasic → Tert-butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

HRID 517981ノート

反応式

HRID 517981 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:28]=[CH:27][C:12]([O:13][CH2:14][CH2:15][CH:16]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]3)=[C:11]([C:29]([F:32])([F:31])[F:30])[CH:10]=2)O1.[NH2:34][C:35]1[C:36]([C:44]#[N:45])=[N:37][C:38](Cl)=[CH:39][C:40]=1[NH:41][CH3:42].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CCOC(C)=O.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].C(Cl)Cl.O>[NH2:34][C:35]1[C:40]([NH:41][CH3:42])=[CH:39][C:38]([C:9]2[CH:28]=[CH:27][C:12]([O:13][CH2:14][CH2:15][CH:16]3[CH2:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:19]3)=[C:11]([C:29]([F:31])([F:32])[F:30])[CH:10]=2)=[N:37][C:36]=1[C:44]#[N:45]

参加物

10

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575713-Amino-6-chloro-4-methylamino-pyridine-2-carbonitrileHCID 67294290Tert-butyl 3-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

生成物 1

HCID 67294695Tert-butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

試薬・触媒・溶媒 5

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of tert-butyl 3-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate (413 mg) in dioxane (3 ml) was added to a flask charged with 3-amino-6-chloro-4-(methylamino)picolinonitrile (160 mg), tris(dibenzylideneacetone)dipalladium (0) (40.1 mg), tricyclohexylphosphine (29.5 mg) and potassium phosphate (372 mg). Water (1.2 ml) was added and the reaction was placed under a nitrogen atmosphere and heated to 100° C. for 2 hours. The mixture was allowed to cool to room temperature then diluted with EtOAc (150 ml) filtered through celite and washed with water (2×100 ml) and brine (50 ml). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure to afford crude product as a brown oil. Purification by flash chromatography (50 g silica column, DCM to 5% MeOH in DCM mobile phase) afforded product still containing minor impurities. DCM was added to the residue causing solid to crash out of solution. The solid was collected by filtration and washed with ether to yield desired product tert-butyl 3-(2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate.

後処理

  1. temperatureto cool to room temperature
  2. filtrationfiltered through celite
  3. washwashed with water (2×100 ml) and brine (50 ml)
  4. dry with materialOrganics were dried over sodium sulphate and solvent
  5. customevaporated under reduced pressure
  6. customto afford crude product as a brown oil
  7. customPurification by flash chromatography (50 g silica column, DCM to 5% MeOH in DCM mobile phase)
  8. customafforded product
  9. additionstill containing minor impurities
  10. filtrationThe solid was collected by filtration
  11. washwashed with ether

出典と根拠

ORDレコード
ord-5452c535990c4e6f885b5556cd67f6fd
出典データセット
uspto-grants-2015_08
特許番号
US09115126B2

反応ノート

読み込み中…