Sodium Hydroxide → Sodium 5-(3,3-dimethylbut-1-ynyl)-3-(4-methyl-N-(4-(4-(pyrrolidine-1-carbonyl)pyridin-2-yloxy)cyclohexyl)cyclohexanecarboxamido)thiophene-2-carboxylate

HRID 1046431ノート

反応式

HRID 1046431 の反応式
[H-].[Na+:2].[CH3:3][C:4]([CH3:33])([CH3:32])[C:5]#[C:6][C:7]1[S:11][C:10]([C:12]([OH:14])=[O:13])=[C:9]([N:15]([CH:25]2[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]2)[C:16]([CH:18]2[CH2:23][CH2:22][CH:21]([CH3:24])[CH2:20][CH2:19]2)=[O:17])[CH:8]=1.Cl[C:35]1[CH:40]=[C:39]([C:41]([N:43]2[CH2:47][CH2:46][CH2:45][CH2:44]2)=[O:42])[CH:38]=[CH:37][N:36]=1.[OH-].[Na+]>C1COCC1.C(OCC)C>[CH3:33][C:4]([CH3:32])([CH3:3])[C:5]#[C:6][C:7]1[S:11][C:10]([C:12]([O-:14])=[O:13])=[C:9]([N:15]([CH:25]2[CH2:30][CH2:29][CH:28]([O:31][C:37]3[CH:38]=[C:39]([C:41]([N:43]4[CH2:47][CH2:46][CH2:45][CH2:44]4)=[O:42])[CH:40]=[CH:35][N:36]=3)[CH2:27][CH2:26]2)[C:16]([CH:18]2[CH2:23][CH2:22][CH:21]([CH3:24])[CH2:20][CH2:19]2)=[O:17])[CH:8]=1.[Na+:2]

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 24798764VX-222HCID 25219248(2-Chloropyridin-4-yl)(pyrrolidin-1-yl)methanone

生成物 1

HCID 66849716Sodium 5-(3,3-dimethylbut-1-ynyl)-3-(4-methyl-N-(4-(4-(pyrrolidine-1-carbonyl)pyridin-2-yloxy)cyclohexyl)cyclohexanecarboxamido)thiophene-2-carboxylate収率 16%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

NaH (50 mg of a 60% oil dispersion, 1.14 mmol) was added in portions to a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (128 mg, 0.287 mmol) and (2-chloro-pyridin-4-yl)-pyrrolidin-1-yl-methanone from the previous step (300 mg, 1.42 mmol) in THF (5.0 mL) at 0° C. After 5 min the reaction was warmed to room temperature and then heated at 85° C. overnight. The reaction was cooled, aqueous NaOH (0.5 mL of a 1.0 N solution) was added and the reaction evaporated to dryness to give a solid residue. The solid was suspended in ethyl ether and sonicated for several minutes. The ether layer was removed to give an orange solid that was dried under vacuum and purified by column chromatography on reverse phase C18 silica gel (100% water to 20% acetonitrile/water). Fractions containing product were pooled and lyophilized to give the desired product as a colorless solid (30 mg, 16%). MS (m/z): 618.0 [M−H]−; HPLC retention time: 6.43 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

後処理

  1. temperatureheated at 85° C. overnight
  2. temperatureThe reaction was cooled
  3. customthe reaction evaporated to dryness
  4. customto give a solid residue
  5. customsonicated for several minutes
  6. customThe ether layer was removed
  7. customto give an orange solid
  8. customthat was dried under vacuum
  9. custompurified by column chromatography on reverse phase C18 silica gel (100% water to 20% acetonitrile/water)
  10. additionFractions containing product

出典と根拠

ORDレコード
ord-49dce2864139486d8e3538a65f2f62ac
出典データセット
uspto-grants-2013_10
特許番号
US08569302B2

反応ノート

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