Pyridine → tert-Butyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl oxalate

HRID 1916370노트

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HRID 1916370 반응식
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[C:7]([OH:11])([CH3:10])([CH3:9])[CH3:8].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[S:27][C:26]3[C:25](=[O:28])[N:24]([C:29]4[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]([OH:40])([CH3:39])[CH3:38])=[C:31]([O:41][CH3:42])[CH:30]=4)[CH:23]=[N:22][C:21]=3[CH:20]=2)=[CH:15][CH:14]=1.COC1C=C([N+]([O-])=O)C=CC=1OCC(C)(O)C.N1C=CC=CC=1>C(Cl)Cl>[C:1]([O:11][C:7]([CH3:10])([CH3:9])[CH3:8])(=[O:5])[C:2]([O:40][C:37]([CH3:39])([CH3:38])[CH2:36][O:35][C:32]1[CH:33]=[CH:34][C:29]([N:24]2[C:25](=[O:28])[C:26]3[S:27][C:19]([C:16]4[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][CH:15]=4)=[CH:20][C:21]=3[N:22]=[CH:23]2)=[CH:30][C:31]=1[O:41][CH3:42])=[O:3]

참가 물질

7

반응물 5

HCID 1049PyridineHCID 6386tert-ButanolHCID 65578Oxalyl chlorideHCID 167186196-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-oneHCID 588580781-(2-Methoxy-4-nitrophenoxy)-2-methylpropan-2-ol

생성물 1

HCID 58858061tert-Butyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl oxalate수율 94%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To oxalyl chloride (0.50 mL; 5.91 mmol) cooled to 0° C. was added t-butanol (0.28 mL; 2.95 mmol) over 30 min. After warming the solution to rt and concentration under reduced pressure, the residue was dissolved in 1 mL of CH2Cl2 whereupon 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]-pyrimidin-4(3H)-one (100 mg; 0.219 mmol) (the product of Example 82) and pyridine (42 uL; 0.522 mmol) were added. After the suspension was stirred at rt for 1.5 h, the solution was diluted with CH2Cl2, washed with 1N HCl and brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 1:1 gradient) to afford 120 mg (94%) of the title compound as a white foam. 1H NMR (CDCl3) δ 1.55 (s, 9H), 1.70 (s, 6H), 3.87 (s, 3H), 4.24 (s, 2H), 6.92 (dd, J=8.25 Hz, 2.20 Hz, 1H), 6.96 (d, J=2.20 Hz, 1H), 7.04 (d, J=8.24 Hz, 1H), 7.44 (d, J=8.79 Hz, 2H), 7.53 (s, 1H), 7.65 (d, J=8.79 Hz, 2H), 8.13 (s, 1H); 13C NMR (CDCl3) δ 23.14, 27.74, 56.36, 74.39, 84.26, 84.51, 111.76, 115.30, 119.27, 120.84, 123.22, 127.65, 129.47, 130.78, 131.54, 135.67, 148.19, 149.25, 150.64, 151.63, 156.77, 157.22, 157.35, 157.60; HPLC (Method #1) 4.40 min retention time, (100%); MS (ES): m/z 585 [M+H]+.

후처리

  1. concentrationconcentration under reduced pressure
  2. additionwere added
  3. washwashed with 1N HCl and brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 1:1 gradient)

출처 및 근거

ORD 기록
ord-3483b019068a4aae92a7e3c90f30fd70
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618115B2

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