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

HRID 2237630Notes

Reaction equation

HRID 2237630 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8900HeptaneSolventHCID 178508906HCID 178508906, compoundSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-76521802846e4ca3acc1f88eb4436c47
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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