5-Bromopyrimidine → 4-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 547914

反応式

HRID 547914 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH2:21])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].O(C(C)(C)C)[K]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

参加物

7

反応物 3

HCID 783445-BromopyrimidineHCID 12682914-Amino-1-Boc-piperidineHCID 178418922HCID 178418922、化合物

生成物 1

HCID 671982114-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl ester収率 47%

試薬・触媒・溶媒 3

HCID 634876Binap, (A+-)-触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

A mixture of 5-bromo-pyrimidine (1.59 g, 10.00 mmol, 1.0 equiv; commercially available), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.00 g, 10.00 mmol, 1.0 equiv), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.25 g, 0.40 mmol, 0.04 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.21 g, 0.20 mmol, 0.02 equiv) and KOtert-Bu (1.35 g, 12.01 mmol, 1.2 equiv) in toluene (10 mL) was heated under Ar by microwave irradiation to 100° C. for 2 h. The crude reaction mixture was filtered through Hyflo Super Cel, a sat. solution of sodium chloride (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL). The combined organic phases were concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane (+1% triethylamine)/ethyl acetate to provide 1.30 g (47%) of the title compound. MS (ISP): 279.1 [M+H]+.

後処理

  1. customThe crude reaction mixture
  2. filtrationwas filtered through Hyflo Super Cel
  3. additiona sat. solution of sodium chloride (100 mL) was added
  4. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic phases were concentrated by evaporation under reduced pressure
  6. customthe residue purified by silica column chromatography
  7. washeluting with a gradient of heptane (+1% triethylamine)/ethyl acetate

出典と根拠

ORDレコード
ord-3f32390041ba44ada63f8874ed90e3fd
出典データセット
uspto-grants-2011_05
特許番号
US07939661B2

関連ノート

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