Sodium Bicarbonate → {4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

HRID 1470827ノート

反応式

HRID 1470827 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:32][O:33][CH:34]1[CH:39]([O:40][CH3:41])[CH:38]([O:42][CH3:43])[CH:37]([CH3:44])[O:36][CH:35]1[O:45][C:46](=O)[O:47]C1C=CC([N+]([O-])=O)=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1.C1(C)C=CC=CC=1>[CH3:32][O:33][C@@H:34]1[C@H:39]([O:40][CH3:41])[C@@H:38]([O:42][CH3:43])[C@H:37]([CH3:44])[O:36][C@H:35]1[O:45][C:46](=[O:47])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[N:14]=2)=[CH:16][CH:17]=1

参加物

7

反応物 4

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 67519234Carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterHCID 675194204-[2-(4-Methoxyphenyl)-pyrimidin-4-yl]-phenylamine

生成物 1

HCID 44230218{4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester収率 8.1%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a mixture cooled in an ice bath of 112 mg (0.404 mmol) of 4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenylamine in 1.5 mL of dry THF was added dropwise via syringe 0.81 mL (0.40 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. This solution was then added dropwise via syringe to a solution cooled in an ice bath of 126 mg (0.386 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of THF. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with ethyl ether and the combined extracts were dried (MgSO4). Concentration gave a red oil which was purified by chromatography on silica gel using 1:1 hexanes/EtOAc to afford 16 mg (8%) of Compound 234. 1H NMR (300 MHz, CDCl3) δ 8.79 (d, J=5.2 Hz, 1H), 8.55 (d, J=8.8 Hz, 2H), 8.25 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.5 Hz, 2H), 7.53 (d, J=5.5 Hz, 1H), 7.05 (d, J=9.0 Hz, 2H), 6.84 (br s, 1H), 6.26 (d, J=1.7 Hz, 1H), 3.92 (s, 3H), 3.71-3.69 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.55-3.47 (m, 1H), 3.24 (t, J=9.4 Hz, 1H), 1.36 (d, J=6.1 Hz, 3H); MS (API-ES+) 510 ([M+H]+, 100).

後処理

  1. additionThis solution was then added dropwise via syringe to a solution
  2. extractionThe mixture was extracted two times with ethyl ether
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. concentrationConcentration
  5. customgave a red oil which
  6. customwas purified by chromatography on silica gel using 1:1 hexanes/EtOAc

出典と根拠

ORDレコード
ord-6674e9ffb3db4190a6211f5f0ca4c85b
出典データセット
uspto-grants-2015_04
特許番号
US09006468B2

反応ノート

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