Sodium bis(trimethylsilyl)amide → HCID 68881254, compound

HRID 1785099Notes

Reaction equation

HRID 1785099 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:26][C:27]1[CH:36]=[C:35]([C:37]#[C:38][CH2:39][O:40][CH3:41])[C:30]2[O:31][CH:32](N)[O:33][C:29]=2[CH:28]=1.C[Si]([N-:46][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[O:24]=[S:21]1(=[O:25])[CH2:22][CH2:23][N:18]([CH2:17][CH2:16][CH2:15][O:14][C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:46][C:28]4[C:29]5[O:33][CH2:32][O:31][C:30]=5[C:35]([C:37]#[C:38][CH2:39][O:40][CH3:41])=[CH:36][C:27]=4[F:26])=[N:3][CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 219360004-Chloro-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazolineHCID 69069580HCID 69069580, compound

Product 1

HCID 68881254HCID 68881254, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared using the method described in example 4 using 4-chloro-7-[3-(1,1-dioxidothiomorpholin-4-yl)propoxy]-6-methoxyquinazoline (150 mg, 0.39 mmol), 5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxolamine (91 mg, 0.41 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 0.82 ml) in DMF (2.5 ml). The crude product was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent. There was thus obtained the title compound (194 mg, 87%) as a colourless solid; NMR Spectrum:DMSOd6) 1.98 (quintet, 2H), 2.66 (t, 2H), 2.92 (m, 4H), 3.21 (m, 4H), 3.36 (s, 3H), 3.94 (s, 3H), 4.20 (t, 2H), 4.37 (s, 2H), 6.16 (s, 2H), 6.91 (d, 1H), 7.23 (s, 1H), 7.81 (s, 1H), 8.36 (s, 1H), 9.52 (s, 1H); Mass Spectrum: M+H+ 573.

Workup

  1. customThis was prepared
  2. customThe crude product was purified by column chromatography on silica using
  3. temperatureincreasing concentrations of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-2d15ad3c88c042edbba2f2e018d07877
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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