Potassium Phosphate, Tribasic → 6-chloro-5-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 73737ノート

反応式

HRID 73737 の反応式
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[C:29](I)=[CH:28][C:13]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)=[O:15])=[CH:12][N:11]=1.[CH3:31][C:32]1[CH:33]=[N:34][N:35]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][O:47]2)[C:36]=1B1OC(C)(C)C(C)(C)O1>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:9][C:10]1[C:29]([C:36]2[N:35]([CH:46]3[CH2:51][CH2:50][CH2:49][CH2:48][O:47]3)[N:34]=[CH:33][C:32]=2[CH3:31])=[CH:28][C:13]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)=[O:15])=[CH:12][N:11]=1

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 547724154-methyl-1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

生成物 1

HCID 867025986-chloro-5-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

K3PO4 (127 mg, 0.6 mmol) was added to a solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 4.2, 89 mg, 0.2 mmol) and 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58.4 mg, 0.2 mmol) in dioxane (1 mL) in a vial which was flushed with argon, heated to 110° C. and then PdCl2(dppf) (7.32 mg, 0.01 mmol) was added. The vial was sealed and the RM was stirred under argon at 110° C. for 18 h. The RM was cooled to RT, dissolved in EtOAc and washed with brine. The organic phase was dried over Na2SO4 and the solvent was evaporated off under reduced pressure. and the residue was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc form 50% to 100% EtOAc) to afford the title compound as a white foam. HPLC (Condition 4) tR=6.24 min, UPLC-MS (Condition 3) tR=1.22 min, m/z=481.2 [M+H]+.

後処理

  1. customwas flushed with argon
  2. customThe vial was sealed
  3. temperatureThe RM was cooled to RT
  4. washwashed with brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customand the residue was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc form 50% to 100% EtOAc)

出典と根拠

ORDレコード
ord-471cd0d48265468c936cdb26f2987c9e
出典データセット
uspto-grants-2014_09
特許番号
US08829195B2

反応ノート

読み込み中…