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

HRID 1948965Notes

Reaction equation

HRID 1948965 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.[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>>[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][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 685201434-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline

Product 1

HCID 600366954-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-2-yl]methoxy}quinazolineYield 50%

Procedure

Using a procedure similar to that described in Example 43, 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(chloroacetyl)pyrrolidin-2-yl]methoxy}quinazoline (0.28 g) was reacted with pyrrolidine (2.5 ml) to give the title product as a foam (0.151 g, 50%); 1H NMR Spectrum: (CDCl3) 1.68-1.75 (m, 4H), 1.90-2.01 (m, 1H), 2.04-2.14 (m, 2H), 2.15-2.23 (m, 1H), 2.51-2.61 (m, 2H), 2.66-2.74 (m, 2H), 3.15-3.21 (d, 1H), 3.38-3.48 (m, 2H), 3.55-3.62 (m, 1H), 4.00-4.08 (m, 4H), 4.52-4.55 (d, 1H), 4.68-4.74 (t, 1H), 7.06-7.27 (m, 3H), 7.90-7.96 (m, 1H), 8.43 (s, 1H), 8.60 (s, 1H), 8.69 (s, 1H); Mass Spectrum: (M−H)− 512.

Sources & evidence

ORD record
ord-8bbbe0b7c3254e8b883db1d000b253d0
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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