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 1916370Notes

Reaction equation

HRID 1916370 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-3483b019068a4aae92a7e3c90f30fd70
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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