Cesium carbonate → (R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-methyloxetan-3-ylmethyl ester

HRID 1907320ノート

反応式

HRID 1907320 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21]([OH:23])=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:24]([C:27]2[CH:28]=[N:29][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:31][CH:32]=2)(=[O:26])=[O:25])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:45][C:46]1([CH3:51])[CH2:49][O:48][CH:47]1Br>CN(C)C=O.O>[CH3:45][C:46]1([CH2:51][O:22][C:21]([C@@:19]23[CH2:18][N:17]([S:24]([C:27]4[CH:28]=[N:29][C:30]([N:33]5[CH2:38][CH2:37][O:36][CH2:35][CH2:34]5)=[CH:31][CH:32]=4)(=[O:25])=[O:26])[CH2:16][CH2:15][C:14]2=[CH:13][C:12]2[N:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[N:9]=[CH:10][C:11]=2[CH2:20]3)=[O:23])[CH2:49][O:48][CH2:47]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 66780217(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acidHCID 681941973-Methyl-3-methylbromo-oxetane

生成物 1

HCID 66779946(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-methyloxetan-3-ylmethyl ester収率 19.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of (R)-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid (0.09 g) in N,N-dimethylformamide (1 mL) was treated with cesium carbonate (0.16 g) and 3-methyl-3-methylbromo-oxetane (0.14 g) at room temperature for 30 minutes. The reaction mixture was diluted with water and the precipitate collected by filtration and dried under vacuum. The solid was purified by preparative reverse-phase HPLC eluting with a mixture of methanol and water containing 0.1% formic acid (3:2 to 4:1 by volume) to give the title compound as a white solid (0.02 g). 1H NMR (400 MHz, CHCl3-d): δ 8.53 (d, 1H), 7.78 (dd, 1H), 7.49-7.41 (m, 3H), 7.16 (t, 2H), 6.62 (d, 1H), 6.45 (s, 1H), 4.49-4.38 (m, 3H), 4.34 (dd, 2H), 4.15 (s, 2H), 3.81 (t, 4H), 3.67 (t, 4H), 3.32 (d, 1H), 2.91 (d, 1H), 2.62 (d, 1H), 2.52 (d, 1H), 2.40 (d, 2H), 1.28 (s, 3H).

後処理

  1. filtrationthe precipitate collected by filtration
  2. customdried under vacuum
  3. customThe solid was purified by preparative reverse-phase HPLC
  4. washeluting with a mixture of methanol and water containing 0.1% formic acid (3:2 to 4:1 by volume)

出典と根拠

ORDレコード
ord-a70f93ab801a495fb9c35697b05e6e5e
出典データセット
uspto-grants-2013_12
特許番号
US08598154B2

反応ノート

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