Sodium Carbonate → (R)-4-((R)-1-(7-(1,2,3,4-tetrahydroisoquinolin-7-yl)quinolin-5-yloxy)ethyl)pyrrolidin-2-one

HRID 1496872ノート

反応式

HRID 1496872 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][C@@H:13]([C@H:15]2[CH2:19][NH:18][C:17](=[O:20])[CH2:16]2)[CH3:14])[CH:3]=1.C(OC([N:28]1[CH2:37][CH2:36][C:35]2[C:30](=[CH:31][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:34]=2)[CH2:29]1)=O)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH2:29]1[C:30]2[C:35](=[CH:34][CH:33]=[C:32]([C:2]3[CH:11]=[C:10]4[C:5]([CH:6]=[CH:7][CH:8]=[N:9]4)=[C:4]([O:12][C@@H:13]([C@H:15]4[CH2:19][NH:18][C:17](=[O:20])[CH2:16]4)[CH3:14])[CH:3]=3)[CH:31]=2)[CH2:36][CH2:37][NH:28]1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 53302321tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 71238288(R)-4-((R)-1-(7-bromoquinolin-5-yloxy)ethyl)pyrrolidin-2-one

生成物 1

HCID 71238155(R)-4-((R)-1-(7-(1,2,3,4-tetrahydroisoquinolin-7-yl)quinolin-5-yloxy)ethyl)pyrrolidin-2-one収率 43.3%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

150 mg Example 27, 241 mg 7-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester, 15 mg bis(triphenylphosphine)palladium(II) chloride, 671 μL 2N aqueous sodium carbonate and 2 mL DMF were heated for 2 hours at 90° C. The mixture was partitioned between DCM and NaHCO3 (sat aq) and the organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue was dissolved in 10 ml 25% TFA in DCM and stirred at 25° C. overnight then concentrated in vacuo. Purification by flash chromatography using 0-25% MeOH/DCM gave 75 mg (43%) of Example 101 (R)-4-{(R)-1-[7-(1,2,3,4-Tetrahydroisoquinolin-7-yl)-quinolin-5-yloxy]-ethyl}-pyrrolidin-2-one as yellow solid.

後処理

  1. customwere heated for 2 hours at 90° C
  2. customThe mixture was partitioned between DCM and NaHCO3 (sat aq)
  3. customthe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 10 ml 25% TFA in DCM
  8. concentrationthen concentrated in vacuo
  9. customPurification by flash chromatography

出典と根拠

ORDレコード
ord-66d2c6a8262b4821b9a867cf7aad44a4
出典データセット
uspto-grants-2015_12
特許番号
US09199937B2

反応ノート

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