Sodium Bicarbonate → 4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(pyrrolidin-1-yliminomethyl)quinazoline

HRID 1801877Notes

Reaction equation

HRID 1801877 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH:28]=O)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.Cl.[NH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH:28]=[N:31][N:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 3017392Pyrrolidin-1-amine monohydrochlorideHCID 577336564-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino) 6-formylquinazoline

Product 1

HCID 687525534-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(pyrrolidin-1-yliminomethyl)quinazolineYield 81.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a mixture of 1 mL of tetrahydrofuran and 0.1 mL of water were dissolved 40 mg of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino) 6-formylquinazoline (IV-1) and 13 mg of 1-amino-pyrrolidine hydrochloride, followed by a reaction at room temperature overnight. After the reaction, aqueous saturated sodium bicarbonate solution was added, followed by extraction with ethyl acetate. The organic layer was dehydrated by passing through Presep (registered trademark), and the filtrate was concentrated. The concentrated residue was purified by chromatography (eluting with hexane:ethyl acetate-2:1→1:1) using an amino column to obtain 38 mg of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(pyrrolidin-1-yliminomethyl)quinazoline (IX-1) as a yellow solid.

Workup

  1. customfollowed by a reaction at room temperature overnight
  2. additionwas added
  3. extractionfollowed by extraction with ethyl acetate
  4. concentrationthe filtrate was concentrated
  5. customThe concentrated residue was purified by chromatography (eluting with hexane:ethyl acetate-2:1→1:1)

Sources & evidence

ORD record
ord-ce1e43eb3af74c7e9c493e2c7bbbe257
Source dataset
uspto-grants-2013_01
Patent number
US08349857B2

Reaction notes

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