Cesium carbonate → Methyl 2-((3-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylate

HRID 1662856ノート

反応式

HRID 1662856 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=1.Br[C:13]1[CH:14]=[C:15]([CH:24]=[CH:25][CH:26]=1)[O:16][CH2:17][CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[N:19]1([CH2:18][CH2:17][O:16][C:15]2[CH:14]=[C:13]([NH:1][C:2]3[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:7]=3)[CH:26]=[CH:25][CH:24]=2)[CH2:23][CH2:22][CH2:21][CH2:20]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 211452Pyrrolidine, 1-(2-(m-bromophenoxy)ethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 9793866Methyl 2-aminopyrimidine-5-carboxylate

生成物 1

HCID 59652715Methyl 2-((3-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylate収率 104.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

Two 20 mL microwave vials were each charged with methyl 2-aminopyrimidine-5-carboxylate (460.0 mg, 3.0 mmol), 1-[2-(3-bromo-phenoxy)-ethyl]-pyrrolidine (811.0 mg, 3.0 mmol), Pd2(dba)3 (110.0 mg, 0.12 mmol), XantPhos (208.3 mg, 0.36 mmol), Cs2CO3 (1.95 g, 6.0 mmol) and anhydrous dioxane (20 mL). The mixture was purged with argon gas for 15 min, then sealed and irradiated in a microwave (Initiator, Biotage) at 180° C. for 60 min. After cooling to room temperature, the cap was removed and the reaction mixtures were combined and partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (3×100 mL). Combined EtOAc solutions were washed with H2O (2×100 mL), brine (2×100 mL) and dried over anhydrous Na2SO4. The resulting solution was concentrated in vacuo with ca. 15 g of silica gel. The loaded silica gel was taken to the ISCO system for further purification (80 g column, solid method, 0% to 20% MeOH gradient in DCM, 40 min method). Fractions, containing the product, were combined and concentrated in vacuo to give reddish oil. The oil was re-crystallized from 10 mL of CH3CN to give the title compound as a light-yellow solid (1.07 g, 35% yield).

後処理

  1. customThe mixture was purged with argon gas for 15 min
  2. customsealed
  3. customirradiated in a microwave (Initiator, Biotage) at 180° C. for 60 min
  4. customthe cap was removed
  5. customthe reaction mixtures
  6. custompartitioned between EtOAc and H2O
  7. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
  8. washCombined EtOAc solutions were washed with H2O (2×100 mL), brine (2×100 mL)
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationThe resulting solution was concentrated in vacuo with ca. 15 g of silica gel
  11. customThe loaded silica gel was taken to the ISCO system for further purification (80 g column, solid method, 0% to 20% MeOH gradient in DCM, 40 min method)
  12. additionFractions, containing the product
  13. concentrationconcentrated in vacuo
  14. customto give reddish oil
  15. customThe oil was re-crystallized from 10 mL of CH3CN

出典と根拠

ORDレコード
ord-222fe0b069594ba186dfac5e8779f6d5
出典データセット
uspto-grants-2011_10
特許番号
US08030487B2

反応ノート

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