Cesium carbonate → (NZ,3R)-N-[3-(3,5-dichlorophenyl)-5-(hydroxymethyl)-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

HRID 390723

反応式

HRID 390723 の反応式
[F:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([NH:9][C:10]2[S:11][C:12]([CH2:15][OH:16])=[CH:13][N:14]=2)=[O:8])[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1CCCCC1C(OCC)=O.[Cl:34][C:35]1[CH:40]=[C:39](I)[CH:38]=[C:37]([Cl:42])[CH:36]=1.[OH-].[NH4+]>CS(C)=O.[Cu](I)I>[Cl:34][C:35]1[CH:40]=[C:39]([N:14]2[CH:13]=[C:12]([CH2:15][OH:16])[S:11]/[C:10]/2=[N:9]\[C:7]([N:4]2[CH2:5][CH2:6][C@@H:2]([F:1])[CH2:3]2)=[O:8])[CH:38]=[C:37]([Cl:42])[CH:36]=1

参加物

8

反応物 5

HCID 10796Cesium carbonateHCID 14923Ammonium HydroxideHCID 18686Ethyl cyclohexanoateHCID 764241,3-Dichloro-5-iodobenzeneHCID 86631927(3R)-3-fluoro-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]pyrrolidine-1-carboxamide

生成物 1

HCID 87638979(NZ,3R)-N-[3-(3,5-dichlorophenyl)-5-(hydroxymethyl)-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 679Dimethyl Sulfoxide溶媒2 回

実験手順

In a 4 mL vial charged with a stir bar, (3R)-3-fluoro-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]pyrrolidine-1-carboxamide (43 mg, 0.18 mmol, Example 36B) was added followed by copper iodide (8 mg, 0.04 mmol) and cesium carbonate (88 mg, 0.27 mmol). A loose cap with septum was placed on the vial and then the vial was placed under vacuum for 30 minutes. The solid mixture was purged with nitrogen gas a couple of times. Then ethyl 2-cyclohexanecarboxylate (12 mg, 0.07 mmol) dissolved in dry dimethyl sulfoxide (0.4 mL) was added to the mixture followed by 1,3-dichloro-5-iodobenzene (60 mg, 0.22 mmol) dissolved in dry dimethyl sulfoxide (0.7 mL). The vial was capped and the resulting mixture was shaken at room temperature for 1 hour followed by shaking at 95° C. overnight. Then 1 mL of concentrated ammonium hydroxide solution was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C18, gradient 10-95% acetonitrile/water/0.1% trifluoroacetic acid) to provide the title compound.

後処理

  1. additionIn a 4 mL vial charged with a stir bar
  2. customA loose cap with septum
  3. customThe solid mixture was purged with nitrogen gas a couple of times
  4. additionwas added to the mixture
  5. customThe vial was capped
  6. stirringby shaking at 95° C. overnight
  7. filtrationThe reaction was filtered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by reverse phase HPLC (C18, gradient 10-95% acetonitrile/water/0.1% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-e56755ecbb2b4532a6f314f11f028c5e
出典データセット
uspto-grants-2013_02
特許番号
US08383657B2

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