Potassium Phosphate, Tribasic → HCID 68328004、化合物

HRID 634307ノート

反応式

HRID 634307 の反応式
[CH:1]([NH:4][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)([CH3:3])[CH3:2].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:73]1[N:78]=[C:77]([CH:79]2[CH2:81][CH2:80]2)[C:76]([C:82]([O:84][CH3:85])=[O:83])=[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[C:76]([C:82]([O:84][CH3:85])=[O:83])=[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]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=4)(=[O:20])=[O:21])[CH:14]=3)[N:78]=2)[CH2:80][CH2:81]1

参加物

6

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68328163HCID 68328163、化合物HCID 83835308Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate

生成物 1

HCID 68328004HCID 68328004、化合物収率 40.3%

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
130 °C

実験手順

A 20 mL microwave vial was charged with N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (300 mg, 0.574 mmol), Xphos (Stem Chemicals, Newburyport, Mass., 16.4 mg, 0.034 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 15.8 mg, 0.017 mmol), methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate (147 mg, 0.689 mmol) and potassium phosphate (366 mg, 1.723 mmol) followed by purging with argon. The solids were treated with dioxane (3 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 (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded methyl 4-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-5-carboxylate (132.4 mg, 0.231 mmol, 40.3% yield) as light yellow amorphous solid. MS (ESI, pos. ion) m/z: 573.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 9.11 (1H, s), 9.04 (1H, d, J=1.2 Hz), 8.59 (1H, s), 8.08 (1H, d, J=8.8 Hz), 8.01 (1H, dd, J=8.8, 1.6 Hz), 7.86 (2H, d, J=8.4 Hz), 7.28 (2H, s), 4.55 (1H, br. s.), 4.00-4.08 (1H, m), 3.98 (3H, s), 3.24-3.34 (1H, m), 2.36 (3H, s), 1.32-1.39 (6H, m), 1.21-1.30 (4H, m).

後処理

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (3 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 (12 g Redisep column

出典と根拠

ORDレコード
ord-ab7f24d6fc9342179b5536322a81867a
出典データセット
uspto-grants-2016_04
特許番号
US09321756B2

反応ノート

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