Acetic Acid → 1-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-2-fluoro-propane-1,3,dione

HRID 1433063Notes

Reaction equation

HRID 1433063 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:29])[CH2:20][C:21]([C:23]4[S:24][C:25]([Cl:28])=[CH:26][CH:27]=4)=[O:22])[CH:15]([CH2:30][CH2:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[H-].[Na+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:46])(=O)=O)=CC=1.C(O)(=O)C>C1COCC1>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:29])[CH:20]([F:46])[C:21]([C:23]4[S:24][C:25]([Cl:28])=[CH:26][CH:27]=4)=[O:22])[CH:15]([CH2:30][CH2:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 588007N-FluorobenzenesulfonimideHCID 872365911-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione

Product 1

HCID 872364831-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-2-fluoro-propane-1,3,dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Prepared by a procedure of Differding and Ofner. (Synlett 1991, 187.). A solution of 1-[4-(4-aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione (0.486 g, 1 mmol) in 40 ml of THF is added dropwise to an ice cold suspension of NaH (0.16 g of 60% NaH, 4 mmol) and 5 ml of THF. After the mixture had stirred one hour at 0° C., a solution of N-fluorobenzenesulfonimide (Aldrich) (0.378 g, 1.2 mmol) in 10 ml of THF is added dropwise. The reaction is stirred overnight at room temperature before quenching with glacial acetic acid (0.23 ml, 0.240 g, 4 mmol). The volatiles are evaporated in vacuo and the residue purified by flash column chromatography eluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2 to provide the product as a white solid. The product could be recrystallized from THF/hexane. M.P. 194-6° C. MS (ion spray) m/z 504, (M+H).

Workup

  1. customPrepared by a procedure of Differding and Ofner
  2. stirringThe reaction is stirred overnight at room temperature
  3. customThe volatiles are evaporated in vacuo
  4. customthe residue purified by flash column chromatography
  5. washeluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2

Sources & evidence

ORD record
ord-a9e62563cb244b6cb3107b7a2730c622
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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