Potassium Carbonate → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(2,3-dihydro-1H-inden-5-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525210ノート

反応式

HRID 525210 の反応式
[CH:1]1([C:4]([N:6]2[CH2:10][CH2:9][C@@H:8]([CH2:11][C:12]3[N:13]([C:18]4[CH:23]=[CH:22][C:21](B5OC(C)(C)C(C)(C)O5)=[CH:20][CH:19]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.Br[C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[CH2:39][CH2:38][CH2:37]2.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].ClCCl>[CH:1]1([C:4]([N:6]2[CH2:10][CH2:9][C@@H:8]([CH2:11][C:12]3[N:13]([C:18]4[CH:23]=[CH:22][C:21]([C:34]5[CH:35]=[C:36]6[C:40](=[CH:41][CH:42]=5)[CH2:39][CH2:38][CH2:37]6)=[CH:20][CH:19]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:2][CH2:3]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 2671395-bromo-2,3-dihydro-1H-indeneHCID 673756365-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 673768325-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(2,3-dihydro-1H-inden-5-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one収率 39%

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.252 mmol) in dioxane (1.5 mL) was treated with 5-bromo-2,3-dihydro-1H-indene (0.252 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.756 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (35-65% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions from the HPLC were combined, adjusted to pH˜5 with the addition of saturated aq sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as an amorphous off-white solid (39%). MS(ES)+ m/e 429.1 [M+H]+.

後処理

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. customirradiated in a microwave (Biotage Initiator) at 150° C. for 15 min
  4. additionwas diluted with water (50 mL)
  5. extractionwas extracted with dichloromethane
  6. additionThe resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by reverse phase HPLC (35-65% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  11. additionadjusted to pH˜5 with the addition of saturated aq sodium bicarbonate
  12. extractionextracted with dichloromethane
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-a8ae61aedad94d45b7d899059d573050
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

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