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Nitrogen → tert-Butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)carbamate

HRID 2175404
ノート
印刷プレビュー

反応式

HRID 2175404 の反応式
Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C@H:10]2[CH2:12][C@@H:11]2[C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][N:14]=2)[N:5]=[C:4]([CH3:20])[N:3]=1.[CH3:21][C:22]1[S:26][C:25]([CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[N:24][N:23]=1.CC(C)([O-])C.[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.N#N>CC(O)(CC)C.C(OCC)(=O)C.C([O-])(O)=O.[Na+].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]>[CH3:21][C:22]1[S:26][C:25]([CH2:27][N:28]([C:2]2[CH:7]=[C:6]([O:8][CH2:9][C@H:10]3[CH2:12][C@@H:11]3[C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][N:14]=3)[N:5]=[C:4]([CH3:20])[N:3]=2)[C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[N:24][N:23]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

10

反応物 5

HCID 947NitrogenHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23665647Potassium tert-butoxideHCID 59892191Tert-butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamateHCID 867295664-chloro-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine

生成物 1

HCID 86729565
tert-Butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)carbamate
収率 70%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 64052-Methyl-2-butanol溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
60 °C

実験手順

A solution of 2-1 (100 mg, 0.35 mmol), tert-butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate (119 mg, 0.52 mmol; for preparation, see D. C. Pryde et al. J. Med. Chem. 2006, 49, 4409-4424), 1 M potassium tert-butoxide (1.03 mL in THF) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.6 mg, 0.035 mmol) in 2-Methyl-2-butanol (1.7 ml) was purged with N2 for 5 min. Tris(dibenzylideneacetone)-dipalladium(0) (31.6 mg, 0.035 mmol) was added and the mixture was heated at 60° C. for 1 hour. The reaction was cooled to room temperature and diluted with ethyl acetate and sat. NaHCO3. The organic phase was washed with water, brine and concentrated. The residue was purified by flash column chromatography using a 20-60% ethyl acetate/hexane gradient gave 2-2 as a colorless oil (117 mg, 70%). MS (M+H)+: observed=483.10, calculated=483.21.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. washThe organic phase was washed with water, brine
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-3d4ea472d1e340ac8194fd53250034c1
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09062059B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート