Triethylamine → (R)-N-(2,2-Dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)-N-(3-methylbutan-2-yl)propanamide

HRID 909905ノート

反応式

HRID 909905 の反応式
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH3:19][N:20]1[CH:24]=[C:23]([C:25]2[CH:26]=[C:27]([CH:36]=[CH:37][CH:38]=2)[CH2:28][CH2:29][O:30][CH2:31][CH2:32][C:33]([OH:35])=O)[CH:22]=[N:21]1.[CH3:39][O:40][CH:41]([O:49][CH3:50])[CH2:42][NH:43][C@@H:44]([CH:46]([CH3:48])[CH3:47])[CH3:45].C(N(CC)CC)C>C1COCC1.C(#N)C.C(OCC)(=O)C>[CH3:39][O:40][CH:41]([O:49][CH3:50])[CH2:42][N:43]([C@@H:44]([CH:46]([CH3:47])[CH3:48])[CH3:45])[C:33](=[O:35])[CH2:32][CH2:31][O:30][CH2:29][CH2:28][C:27]1[CH:36]=[CH:37][CH:38]=[C:25]([C:23]2[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=2)[CH:26]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 58168508(R)-N-(2,2-dimethoxyethyl)-3-methylbutan-2-amineHCID 592904613-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid

生成物 1

HCID 67075774(R)-N-(2,2-Dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)-N-(3-methylbutan-2-yl)propanamide

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
25 °C

実験手順

A solution of T3P (1.86 mL) dissolved in THF (1.57M) was added in one portion to a stirred solution of 3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid [Example 2a, Step i)] (567 mg), (R)—N-(2,2-dimethoxyethyl)-3-methylbutan-2-amine [Preparation 4] (307 mg), and triethylamine (2.44 mL) in acetonitrile (6 mL) at 25° C. The resulting solution was stirred at 25° C. for 15 min. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with saturated sodium hydrogen carbonate (20 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0-100% ethyl acetate in isohexane, then elution gradient 5-10% methanol in ethyl acetate to afford the subtitled compound as a gum (210 mg). 1H NMR (400 MHz, CD3OD) δ 7.92 and 7.91 (2×s, 1H), 7.77 (s, 1H), 7.40-7.37 (m, 1H), 7.36-7.32 (m, 1H), 7.23 and 7.22 (2×t, J=7.7 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 4.59 and 4.43 (2×t, J=5.4 Hz, 1H), 3.90 (s, 3H), 3.75-3.45 (m, 5H), 3.36 (d, J=1.5 Hz, 2H), 3.35, 3.34, 3.33, 3.32 (4×s, 6H), 2.84 and 2.84 (2×t, J=7.0 Hz, 2H), 2.76-2.61 (m, 2H), 1.98-1.86 and 1.79-1.66 (2×m, 1H), 1.16 and 1.14 (2×d, J=7.0 Hz, 3H), 0.90 and 0.88 (2×d, J=6.8 Hz, 3H), 0.79 and 0.75 (2×d, J=6.8 Hz, 3H), a ˜1:1 mixture of rotamers is observed.

後処理

  1. washwashed with saturated sodium hydrogen carbonate (20 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0-100% ethyl acetate in isohexane
  7. washelution gradient 5-10% methanol in ethyl acetate

出典と根拠

ORDレコード
ord-2a68b9b72bb94af0b95512feabbe503e
出典データセット
uspto-grants-2011_09
特許番号
US08017602B2

反応ノート

読み込み中…