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Potassium Phosphate, Tribasic → 2-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazole

HRID 634219
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HRID 634219 반응식
[CH2:1]([C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3B2OC(C)(C)C(C)(C)O2)=[N:8][N:9]=1)[CH:2]([CH3:4])[CH3:3].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:73]1[N:78]=[C:77]([CH:79]2[CH2:81][CH2:80]2)[CH:76]=[CH:75][N:74]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]>[CH:79]1([C:77]2[CH:76]=[CH:75][N:74]=[C:73]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:7]5[O:6][C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:21])=[O:20])[CH:14]=3)[N:78]=2)[CH2:81][CH2:80]1
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6

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 49758247HCID 49758247, 화합물HCID 683281102-isobutyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole

생성물 1

HCID 683284252-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazole
수율 40%

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
130 °C

실험 절차

To a 20 mL microwave vial was added 2-isobutyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (233 mg, 0.530 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (15.2 mg, 0.032 mmol), Pd2(dba)3 (14.6 mg, 0.016 mmol), 2-bromo-4-cyclopropylpyrimidine (CombiPhos Catalysts Inc., 121 mg, 0.610 mmol) and potassium phosphate (338 mg, 1.59 mmol) followed by purging with argon. The solids were treated with dioxane (4.0 mL) and water (0.4 mL) and heated in the microwave at 130° C. for 20 min. The mixture was treated with H2O and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification (eluting with 10-60% EtOAc in Hex) afforded 2-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazole (108 mg, 40%) as a light yellow viscous oil. MS (ESI, pos. ion) m/z: 514.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 9.27 (1H, s), 8.50-8.58 (2H, m), 8.09-8.13 (2H, m), 7.86 (2H, d, J=8.4 Hz), 7.24 (2H, s), 7.07 (1H, d, J=5.1 Hz), 2.84 (2H, d, J=7.2 Hz), 2.35 (3H, s), 2.29 (1H, s), 1.91 (1H, br. s.), 1.34-1.40 (2H, m), 1.17 (2H, dd, J=7.8, 2.9 Hz), 1.07 (6H, d, J=6.7 Hz).

후처리

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (4.0 mL) and water (0.4 mL)
  3. additionThe mixture was treated with H2O
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification (eluting with 10-60% EtOAc in Hex)

출처 및 근거

ORD 기록
ord-2e58bccb659842bea6787d367b5a9b0b
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09321756B2

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