Ethyl Acetate → 4-Amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one

HRID 2237630

Reaktionsgleichung

Reaktionsgleichung von HRID 2237630
[Si]([O:8][CH2:9][CH2:10][NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][CH:13]=1)(C(C)(C)C)(C)C.C([N:21](CC)C(C)C)C.Cl[C:28]1[C:33]([C:34](Cl)=[O:35])=[C:32](Cl)[N:31]=[CH:30][N:29]=1.CCOC(C)=O>C1NC2NC(N)=NC(=O)C=2N2C1CN(C1C=CC(C(N[C@H](C(O)=O)CCC(O)=O)=O)=CC=1)C2.CCCCCCC>[NH2:21][C:28]1[C:33]2[C:34](=[O:35])[N:11]([C:12]3[CH:13]=[CH:14][C:15]([I:18])=[CH:16][CH:17]=3)[CH2:10][CH2:9][O:8][C:32]=2[N:31]=[CH:30][N:29]=1

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 521913N,N-Diethyl-2-propanamineHCID 121633604,6-Dichloro-pyrimidine-5-carbonyl chlorideHCID 59302533N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-4-iodoaniline

Produkt 1

HCID 593025304-Amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8900HeptaneLösungsmittelHCID 178508906HCID 178508906, VerbindungLösungsmittel

Versuchsvorschrift

To a cooled (ice/water), stirred solution of N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-iodoaniline (1.34 g, 2.78 mmol) and diethylisopropylamine (0.7 mL, 4.0 mmol) in MTHF (5 mL) was added 4,6-dichloroprimidine-5-carbonyl chloride (560 mg, 2.65 mmol). After 5 minutes, the cooling bath was removed and the slurry was stirred for 5 hours. Aqueous hydrochloric acid (1N, 5 mL) was added and the mixture was allowed to stand for 72 hours. The layers were separated and the aqueous layer was washed with MTHF (2×). The combined organic layers were washed with saturated aqueous sodium bicarbonate, saturated aqueous brine, dried over sodium sulfate and concentrated in vacuo to afford an oil. Chromatography (40 g silica gel column, 20-100% EtOAc:heptane) afforded the title compound, 542 mg. 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 7.62 (d, 2H), 7.17 (d, 2H), 4.07 (t, 2H), 3.91 (q, 2H). m/z=438.0 (M+1).

Aufarbeitung

  1. customthe cooling bath was removed
  2. additionAqueous hydrochloric acid (1N, 5 mL) was added
  3. waitto stand for 72 hours
  4. customThe layers were separated
  5. washthe aqueous layer was washed with MTHF (2×)
  6. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate, saturated aqueous brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto afford an oil

Quellen und Nachweise

ORD-Eintrag
ord-76521802846e4ca3acc1f88eb4436c47
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07718645B2

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