Diisopropylethylamine → (S)-1-{5'-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2'-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid

HRID 640637ノート

反応式

HRID 640637 の反応式
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[O:21]1[C:25]2[CH:26]=[CH:27][C:28]([C:30]3([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH3:52])=[C:40]([C:42]5[CH:47]=[CH:46][C:45]([S:48](Cl)(=[O:50])=[O:49])=[CH:44][CH:43]=5)[CH:41]=4)=[O:34])[CH2:32][CH2:31]3)=[CH:29][C:24]=2[O:23][CH2:22]1.CCN(C(C)C)C(C)C>O1CCOCC1>[O:21]1[C:25]2[CH:26]=[CH:27][C:28]([C:30]3([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH3:52])=[C:40]([C:42]5[CH:47]=[CH:46][C:45]([S:48]([N:1]6[CH2:8][CH2:7][CH2:6][C@H:2]6[C:3]([OH:5])=[O:4])(=[O:49])=[O:50])=[CH:44][CH:43]=5)[CH:41]=4)=[O:34])[CH2:32][CH2:31]3)=[CH:29][C:24]=2[O:23][CH2:22]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 145742L-ProlineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 59205984HCID 59205984、化合物

生成物 1

HCID 59206025(S)-1-{5'-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2'-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

L-Proline (57 mg, 0.50 mmol) was treated with N,O-bis(trimethylsilyl)acetamide (250 μl, 1.0 mmol) in 1 mL dioxane overnight at 50° C. To this mixture was added 5′-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2′-methylbiphenyl-4-sulfonyl chloride (˜35 μmol, 400 μl solution in chloroform) followed by DIEA (100 μL). The reaction mixture was kept at room temperature for 1 h, evaporated, and diluted with DMSO (400 μl). The resulting solution was subjected to preparative HPLC purification. Fractions containing the desired material were combined and concentrated in vacuum centrifuge at 40° C. to provide the trifluoroacetic salt of (S)-1-{5′-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2′-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid. ESI-MS m/z calc. 548.1, found 549.1 (M+1), retention time 3.40 min; 1H NMR (250 MHz, DMSO-d6) δ 1.04 (m. 2H), δ 1.38 (m, 2H), δ 1.60 (m, 1H), δ 1.80-1.97 (m, 3H) δ 2.16 (s, 3H), δ 3.21 (m, 1H), 3.39 (m, 1H), 4.15 (dd, 1H, J=4.1 Hz, J=7.8 Hz), δ 6.01 (s, 2H), δ 6.89 (s, 2H), δ 6.98 (s, 1H), δ 7.21 (d, 1H, J=8.3 Hz), δ 7.45 (d, 1H, J=2 Hz), δ 7.52 (dd, 1H, J=2 Hz, J=8.3 Hz), δ 7.55 (d, 2H, J=8.3 Hz), δ 7.88 (d, 2H, J=8.3 Hz), δ 8.80 (s, 1H).

後処理

  1. customevaporated
  2. additiondiluted with DMSO (400 μl)
  3. customThe resulting solution was subjected to preparative HPLC purification
  4. additionFractions containing the desired material
  5. concentrationconcentrated in vacuum centrifuge at 40° C.

出典と根拠

ORDレコード
ord-7589cf5ad9884ed98d706a06d2d5ce4f
出典データセット
uspto-grants-2010_04
特許番号
US07691902B2

反応ノート

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