Sodium Chloride → 2,2-dimethylmalonic acid 5-{(R)-(4-{amino(2,2-dimethylpropoxycarbonylimino)methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester t-butyl ester

HRID 2089628

反応式

HRID 2089628 の反応式
[CH3:1][C:2]([CH3:46])([CH3:45])[CH2:3][O:4][C:5](=[O:44])[N:6]=[C:7]([NH2:43])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH:15]([C:29]2[N:33]=[C:32]([O:34][CH2:35]Cl)[N:31]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:30]=2)[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH2:25][CH2:26][OH:27])[C:17]=2[F:28])=[CH:10][CH:9]=1.[C:47]([O:51][C:52](=[O:59])[C:53]([CH3:58])([CH3:57])[C:54]([OH:56])=[O:55])([CH3:50])([CH3:49])[CH3:48].[I-].[Na+].C(=O)([O-])O.[K+].[Cl-].[Na+]>C(OCC)(=O)C.O.CC(N(C)C)=O>[C:47]([O:51][C:52](=[O:59])[C:53]([CH3:58])([CH3:57])[C:54]([O:56][CH2:35][O:34][C:32]1[N:31]([C:37]2[N:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[N:30]=[C:29]([C@H:15]([NH:14][C:11]2[CH:12]=[CH:13][C:8]([C:7]([NH2:43])=[N:6][C:5]([O:4][CH2:3][C:2]([CH3:46])([CH3:45])[CH3:1])=[O:44])=[CH:9][CH:10]=2)[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH2:25][CH2:26][OH:27])[C:17]=2[F:28])[N:33]=1)=[O:55])([CH3:50])([CH3:48])[CH3:49]

参加物

9

反応物 5

HCID 5234Sodium ChlorideHCID 5238Sodium IodideHCID 2544153-(Tert-butoxy)-2,2-dimethyl-3-oxopropanoic acidHCID 516893Potassium BicarbonateHCID 67470504[1-amino-1-[4-({(5-chloromethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}amino)phenyl]methylidene]carbamic acid 2,2-dimethylpropyl ester

生成物 1

HCID 682128502,2-dimethylmalonic acid 5-{(R)-(4-{amino(2,2-dimethylpropoxycarbonylimino)methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester t-butyl ester

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

実験手順

A mixture of [1-amino-1-[4-({(5-chloromethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}amino)phenyl]methylidene]carbamic acid 2,2-dimethylpropyl ester (170 mg), 2,2-dimethylmalonic acid mono-t-butyl ester [CAS No. 143688-40-8] (490 mg), sodium iodide (390 mg), potassium hydrogen carbonate (182 mg), and DMA (25 mL) was stirred at 50° C. overnight. After cooling the mixture to room temperature, 1:1 mixture of water and saturated aqueous sodium chloride and ethyl acetate were added thereto, and the resulting mixture was extracted. The aqueous layer was reextracted with ethyl acetate twice. All the organic layers were combined, washed with water, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain a racemate of the captioned compound.

後処理

  1. additionwere added
  2. extractionthe resulting mixture was extracted
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe desiccant was filtered off
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)
  10. customto obtain a racemate of the captioned compound

出典と根拠

ORDレコード
ord-33c42e358211445e8479160002c29b98
出典データセット
uspto-grants-2013_05
特許番号
US08436009B2

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