Sodium bis(trimethylsilyl)amide → 7-[3-(4-acetylpiperazin-1-yl)propoxy]-N-[5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxyquinazolin-4-amine

HRID 1785100Notes

Reaction equation

HRID 1785100 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18](Cl)=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:27][C:28]1[CH:36]=[C:35]([C:37]#[C:38][CH2:39][O:40][CH3:41])[C:31]2[O:32][CH2:33][O:34][C:30]=2[C:29]=1[NH2:42].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18]([NH:42][C:29]4[C:30]5[O:34][CH2:33][O:32][C:31]=5[C:35]([C:37]#[C:38][CH2:39][O:40][CH3:41])=[CH:36][C:28]=4[F:27])=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 589602297-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazolineHCID 688818145-Fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine

Product 1

HCID 688810957-[3-(4-acetylpiperazin-1-yl)propoxy]-N-[5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxyquinazolin-4-amineYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared using the, method described in the example 4 using 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (150 mg, 0.40 mmol), 5-fluoro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (97 mg, 0.43 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 0.83 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 (162 mg, 72%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 1.98 (quintet, 2H), 1.99 (s, 3H), 2.34 (m, 2H), 2.40 (m, 2H), 2.50 (t, 2H), 3.37 (s, 3H), 3.44 (m, 4H), 3.94 (s, 3H), 4.20 (t, 2H), 4.37 (s, 2H), 6.16 (s, 2H), 6.91 (d, 1H), 7.19 (s, 1H), 7.81 (s, 1H), 8.36 (s, 1H), 9.52 (s, 1H); Mass Spectrum: M+H+ 566.

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-91553e00759a490f9aba0023e4e56409
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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