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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
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HRID 2085092 반응식
[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]
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참가 물질

7

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

생성물 1

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

시약·촉매·용매

2
HCID 6228Dimethylformamide용매HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8e83e10ddcd84bd0a1b9e1667fd90f79
출처 데이터셋
uspto-grants-2004_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06720322B2

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