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Citric Acid → 4-tert-Butyl-N-[6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzenesulfonamide

HRID 2085092
ノート
印刷プレビュー

反応式

HRID 2085092 の反応式
[H-].[Na+].[CH2:3]([OH:8])[C:4]#[C:5][CH2:6][OH:7].[C:9]([C:13]1[CH:18]=[CH:17][C:16]([S:19]([NH:22][C:23]2[C:28]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[O:36][CH3:37])=[C:27](Cl)[N:26]=[C:25]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[N:24]=2)(=[O:21])=[O:20])=[CH:15][CH:14]=1)([CH3:12])([CH3:11])[CH3:10].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CN1C(=O)N(C)CCC1>[C:9]([C:13]1[CH:14]=[CH:15][C:16]([S:19]([NH:22][C:23]2[C:28]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[O:36][CH3:37])=[C:27]([O:7][CH2:6][C:5]#[C:4][CH2:3][OH:8])[N:26]=[C:25]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[N:24]=2)(=[O:21])=[O:20])=[CH:17][CH:18]=1)([CH3:12])([CH3:10])[CH3:11]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 311Citric AcidHCID 80662-Butyne-1,4-diolHCID 24758Sodium hydrideHCID 227294144-t-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-morpholino-4-pyrimidinyl]benzenesulfonamide

生成物 1

HCID 101885174-tert-Butyl-N-[6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzenesulfonamide収率 16.2%

試薬・触媒・溶媒

2
HCID 6228Dimethylformamide溶媒HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-溶媒

実験手順

To a suspension of 675 mg of NaH in 45 ml of DMF and 5 ml of DMPU was added 4.85 g of 2-butyne-1,4-diol. The mixture was stirred at room temperature until evolution of gas had ceased. Then 1.5 g of 4-tert.-butyl-N-[6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide was added and the resulting mixture was heated to 95° C. and stirred for 5 days. Eventually, the mixture was pourred into 150 ml of 10% aqueous citric acid and extracted three times with 150 ml of ethyl acetate. The organic layers were washed with water and brine, dried over MgSO4 and evaporated. The resulting residue was purified by column chromatography on silicagel eluting with hexane:ethyl acetate 1:1 to give 265 mg of 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide as a beige foam along with 1.13 g of the starting material 4-tert.-butyl-N-[6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide. LC-MS: tR=5.39 min, [M+1]+=583.41, [M−1]−=581.35.

後処理

  1. temperaturethe resulting mixture was heated to 95° C.
  2. stirringstirred for 5 days
  3. extractionextracted three times with 150 ml of ethyl acetate
  4. washThe organic layers were washed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe resulting residue was purified by column chromatography on silicagel
  8. washeluting with hexane:ethyl acetate 1:1

出典と根拠

ORDレコード
ord-8e83e10ddcd84bd0a1b9e1667fd90f79
出典データセット
uspto-grants-2004_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06720322B2

反応ノート

読み込み中…

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