Methylamine → 4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(N-methylaminoacetyl)pyrrolidin-2-yl]methoxy}quinazoline

HRID 1948963Notes

Reaction equation

HRID 1948963 reaction equation
[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[C:23](=[O:26])[CH2:24]Cl)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[CH3:33][NH2:34]>C(O)C>[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[C:23](=[O:26])[CH2:24][NH:34][CH3:33])[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 685201434-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline

Product 1

HCID 100278344-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(N-methylaminoacetyl)pyrrolidin-2-yl]methoxy}quinazolineYield 47%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Using a procedure similar to that described for the synthesis Example 43, 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloracetyl)pyrrolidin-2-yl]methoxy}quinazoline (0.28 g; prepared as described in Example 43, preparation of starting materials) was reacted with 33% methylamine in ethanol (5 ml) to give the title product as a foam (0.131 g, 47%); 1H NMR Spectrum: (CDCl3) 1.91-2.22 (m, 4H), 2.22 (s, 3H), 2.70-2.90 (m, 1H), 3.28-3.40 (m, 2H), 3.44-3.54 (m, 2H), 3.97-4.09 (m, 4H), 4.47-4.51 (d, 1H), 4.60-4.66 (t, 1H), 7.06-7.20 (m, 2H), 7.24 (s, 1H), 8.07-8.13 (m, 1H), 8.57-8.70 (m, 3H); Mass Spectrum: (M−H)− 472.

Sources & evidence

ORD record
ord-ab8e6eb24ab54fff851a9d4cddb48a72
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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