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 1504875노트

반응식

HRID 1504875 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-8505986d6e2540ad83afe5fe9c53072a
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216173B2

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