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

HRID 73737노트

반응식

HRID 73737 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-471cd0d48265468c936cdb26f2987c9e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829195B2

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