Diisopropylethylamine → 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N,1-dimethylpiperidine-4-carboxamide

HRID 1867685Notes

Reaction equation

HRID 1867685 reaction equation
[Cl:1][C:2]1[C:3]([F:34])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:32][CH3:33])=[C:16]([CH2:19][N:20]([CH3:31])[C:21]4([C:28](O)=[O:29])[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.[N:42]1(OC(N(C)C)=[N+](C)C)[C:46]2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN>CN(C)C=O>[Cl:1][C:2]1[C:3]([F:34])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:32][CH3:33])=[C:16]([CH2:19][N:20]([CH3:31])[C:21]4([C:28]([NH:42][CH3:46])=[O:29])[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579798044-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-methylpiperidine-4-carboxylic acid

Product 1

HCID 114970124-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N,1-dimethylpiperidine-4-carboxamideYield 79.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-methylpiperidine-4-carboxylic acid (50 mg, 0.1 mmol) was dissolved in N,N-dimethylformamide (2 ml) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (59 mg, 0.15 mmol) and N,N-diisopropylethylamine (89 μl, 0.51 mmol) were added. After a few minutes methylamine hydrochloride (10 mg, 0.15 mmol) was added and the mixture stirred for 1 hour at room temperature. The mixture was absorbed onto an Isolute SCX column, washed with methanol and eluted with ammonia in methanol. Appropriate fractions were combined and concentrated. The residue was purified by column chromatography on silica, eluting with 5% 7N ammonia in methanol/dichloromethane, to give the title product (40 mg, 77%) as a white solid; 1H NMR Spectrum: (DMSO d6) 1.82 (m, 2H); 2.02 (m, 2H); 2.13 (m, 8H); 2.65 (m, 5H); 3.60 (s, 2H); 3.94 (s, 3H); 7.18 (s, 1H); 7.30 (t, 1H); 7.50 (m, 1H); 7.58 (m, 2H); 8.32 (s, 1H); 8.73 (s, 1H); 9.68 (s, 1H). Mass Spectrum: (M+H)+ 501.

Workup

  1. customThe mixture was absorbed onto an Isolute SCX column
  2. washwashed with methanol
  3. washeluted with ammonia in methanol
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica
  6. washeluting with 5% 7N ammonia in methanol/dichloromethane

Sources & evidence

ORD record
ord-41a48fe96aff4726803e710a79dfad4b
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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