Diisopropylethylamine → 1-[6-nitro-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428872Notes

Reaction equation

HRID 1428872 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N+:31]([O-:33])=[O:32])[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11].[N+](C1C=C2C(=CC=1)N=C(N1C=C(C(O)=O)C=N1)NC2=O)([O-])=O.Cl[CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62]>C1COCC1>[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:29]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62])[C:28](=[O:30])[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N+:31]([O-:33])=[O:32])[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 1360276391-(6-nitro-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acidHCID 1363371881-(6-nitro-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 684879631-[6-nitro-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl esterYield 100.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIEA (4.41 mL, 25.6 mmol) was added to a suspension of 1-(6-nitro-4-oxo-3,4-dihydro-quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate from Example 164, product from Step D) (4.21 g, 12.8 mmol) in THF (64 mL), followed by (2-chloromethoxy-ethyl)-trimethylsilane (2.49 mL, 14.1 mmol). The reaction mixture was stirred at room temperature for 18 h and then concentrated. The residue was partitioned between water (75 mL) and EtOAc (75 mL), and the organic layer was washed with water (2×75 mL) and brine (50 mL), dried (MgSO4), and concentrated to yield the titled compound (5.92 g, 86% yield, 85% pure). This material was carried on to the next step without further purification. MS (ESI/Cl): mass calcd. for C20H25N5O6Si, 459.2; m/z found, 402.1 [M+H−58]+.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between water (75 mL) and EtOAc (75 mL)
  3. washthe organic layer was washed with water (2×75 mL) and brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f887a0e5050848c0b648e324d99061e6
Source dataset
uspto-grants-2015_01
Patent number
US08937078B2

Reaction notes

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