Sodium hydride → (S)-N-(3-ethynylphenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine

HRID 1051234Notes

Reaction equation

HRID 1051234 reaction equation
[H-].[Na+].[O:3]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4]1.[C:9]([C:11]1[CH:12]=[C:13]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24](F)=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:14]=[CH:15][CH:16]=1)#[CH:10]>C1COCC1>[C:9]([C:11]1[CH:12]=[C:13]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:8][C@H:5]4[CH2:6][CH2:7][O:3][CH2:4]4)=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:14]=[CH:15][CH:16]=1)#[CH:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 59142759N-(3-ethynylphenyl)-7-fluoro-6-nitroquinazolin-4-amine

Product 1

HCID 90014153(S)-N-(3-ethynylphenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amineYield 48,370.898%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In an ice bath, NaH (1.87 g, 60%, 0.046 mol) was carefully added into a solution of (S)-tetrahydrofuran-3-ol (3.43 g, 0.039 mmol) in 100 mL anhydrous THF, and stirred for 2 hours at room temperature. Then N-(3-ethynylphenyl)-7-fluoro-6-nitroquinazolin-4-amine (10 g, 0.032 mol) was added and stirred for at 60° C. overnight. The solution was quenched with 1 mL H2O and concentrated, the residue was purified by silica gel column to give (S)—N-(3-ethynylphenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine as yellow solid 7.1 g (58.1% yield).

Workup

  1. stirringstirred for at 60° C. overnight
  2. customThe solution was quenched with 1 mL H2O
  3. concentrationconcentrated
  4. customthe residue was purified by silica gel column

Sources & evidence

ORD record
ord-fb82195618b44d1ebcf7da9ca86e2c94
Source dataset
uspto-grants-2016_07
Patent number
US09388170B2

Reaction notes

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