Tetrahydrofuran → N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(2-morpholin-4-ylethoxy)quinazolin-4-amine

HRID 1785151Notes

Reaction equation

HRID 1785151 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[N:24]=[CH:23][N:22]=[C:21]2OC1C(F)=C(F)C(F)=C(F)C=1F.[Cl:49][C:50]1[CH:58]=[C:57]([C:59]#[C:60][CH2:61][O:62][CH3:63])[C:53]2[O:54][CH2:55][O:56][C:52]=2[C:51]=1[NH2:64].[Cl-].[NH4+]>CN(C)C=O>[Cl:49][C:50]1[CH:58]=[C:57]([C:59]#[C:60][CH2:61][O:62][CH3:63])[C:53]2[O:54][CH2:55][O:56][C:52]=2[C:51]=1[NH:64][C:21]1[C:20]2[C:25](=[CH:26][C:27]([O:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[C:18]([O:17][CH3:16])[CH:19]=2)[N:24]=[CH:23][N:22]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 210827165-Chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amineHCID 227323066-Methoxy-7-(2-morpholin-4-ylethoxy)-4-(pentafluorophenoxy)quinazoline

Product 1

HCID 68884803N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(2-morpholin-4-ylethoxy)quinazolin-4-amineYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.63 ml) in tetrahydrofuran (1.0M, 1.63 mmol) was added dropwise to an ice-cold solution of 6-methoxy-7-(2-morpholin-4-ylethoxy)-4-(pentafluorophenoxy)quinazoline (0.35 g, 0.74 mmol) and 5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (0.213 g, 0.89 mmol) in dimethylformamide (4 ml). The mixture was allowed to warm to room temperature over 3 hours. A saturated solution of ammonium chloride was added and the mixture was partitioned between water and dichloromethane. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. Flash chromatography on silica eluting with a mixture of 2-11% methanol in dichloromethane gave the product as a solid (0.029 g, 8%). NMR Spectrum: (CDCl3) 2.63 (m, 4H), 2.92 (t, 2H), 3.48 (s, 3H), 3.72 (m, 4H), 4.00 (s, 3H), 4.32 (t, 2H), 4.37 (s, 2H), 6.07 (s, 2H), 7.02 (s(broad), 1H), 7.07 (s, 1H), 7.12 (s, 1H), 7.25 (s, 1H), 8.62 (s, 1H). Mass Spectrum: M+H+ 525 and 527.

Workup

  1. customthe mixture was partitioned between water and dichloromethane
  2. customThe organic layer was separated
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. additionFlash chromatography on silica eluting with a mixture of 2-11% methanol in dichloromethane

Sources & evidence

ORD record
ord-7128598e468640a8bbab34775df2d5e7
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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