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Potassium Phosphate, Tribasic → 5-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

HRID 634303
ノート
印刷プレビュー

反応式

HRID 634303 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](B3OC(C)(C)C(C)(C)O3)=[CH:7][N:8]2[S:11]([C:14]2[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][C:3]=1[C:30]1[O:34][C:33]([NH:35][CH:36]([CH3:38])[CH3:37])=[N:32][N:31]=1.Br[C:40]1[N:45]=[C:44]([CH:46]2[CH2:48][CH2:47]2)[CH:43]=[CH:42][N:41]=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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH:46]1([C:44]2[CH:43]=[CH:42][N:41]=[C:40]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[C:3]([C:30]5[O:34][C:33]([NH:35][CH:36]([CH3:37])[CH3:38])=[N:32][N:31]=5)[CH:4]=4)[N:8]([S:11]([C:14]4[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=4)(=[O:12])=[O:13])[CH:7]=3)[N:45]=2)[CH2:48][CH2:47]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 49758247HCID 49758247、化合物HCID 683280445-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

生成物 1

HCID 683288885-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine収率 102.6%

試薬・触媒・溶媒 2

HCID 9811564
Bis(dibenzylideneacetone)palladium
触媒
HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl触媒

反応条件

温度
130 °C

実験手順

A 20 mL microwave vial was charged with 5-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (185 mg, 0.342 mmol), Xphos (Strem Chemicals, Newburyport, Mass., 9.8 mg, 0.021 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 9.4 mg, 10.27 μmol), 2-bromo-4-cyclopropylpyrimidine (CombiPhos Catalysts Inc., Princeton, N.J., 82 mg, 0.411 mmol) and potassium phosphate (218 mg, 1.03 mmol) followed by purging with argon. The solids were treated with dioxane (4.0 mL) and water (1.0 mL) and heated in the microwave at 130° C. for 20 min. The reaction mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded 5-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (186.7 mg, 0.351 mmol, 102% yield) as a viscous yellow oil in ca. 90% purity. MS (ESI, pos. ion) m/z: 533.0 (M+H)+. The material was used in the subsequent step without further purification.

後処理

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (4.0 mL) and water (1.0 mL)
  3. additionThe reaction mixture was treated with water
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column

出典と根拠

ORDレコード
ord-2dd85c3f98714f4eb1823713105e1502
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09321756B2

反応ノート

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