Lithium Hexamethyldisilazide → tert-Butyl{1-[2-(7-methoxy-3-methyl-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 255275Notes

Reaction equation

HRID 255275 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:15])[N:8]([CH3:14])[C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CS(O[CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:35][CH2:34]1)(=O)=O.COC1C=C2C(C=CC(=O)N2CCN2CCC(NC(=O)OC(C)(C)C)CC2)=CC=1>ClCCl.CO>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:15])[N:8]([CH3:14])[C:9](=[O:13])[N:10]2[CH2:31][CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:41])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:35][CH2:34]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 208001227-Methoxy-3-methylquinazoline-2,4(1H,3H)-dione2×HCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×HCID 59371209tert-butyl {1-[2-(7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

Product 1

HCID 86642632tert-Butyl{1-[2-(7-methoxy-3-methyl-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 18.5%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

7-Methoxy-3-methylquinazoline-2,4(1H,3H)-dione (Intermediate 112, 523 mg, 2.5 mmol) was deprotonated with lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 1.9 mL, 1.9 mmol) and alkylated with 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6, 3.4 mmol) as described for Intermediate 2. Chromatography on silica gel with dichloromethane/methanol (95:5) gave 200 mg (18%) of the product as a colorless solid.

Sources & evidence

ORD record
ord-bc6e9354c67e4e80ba9e8a05d0efbb9c
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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