Acetic Acid → {2-Amino-6-[4-fluoro-2-(2-methylpyrrolidin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

HRID 1631135Notes

Reaction equation

HRID 1631135 reaction equation
[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:24]=3[CH:25]=O)[CH:8]=2)[N:3]=1.[CH3:32][CH:33]1[CH2:37][CH2:36][CH2:35][NH:34]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O1CCCC1.O>[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:24]=3[CH2:25][N:34]3[CH2:35][CH2:36][CH2:37][CH:33]3[CH3:32])[CH:8]=2)[N:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 130032-MethylpyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 871741022-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-5-fluorobenzaldehyde

Product 1

HCID 56943242{2-Amino-6-[4-fluoro-2-(2-methylpyrrolidin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

95 mg of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-5-fluorobenzaldehyde are dissolved in 2 ml of 1,2-dichloroethane and 2 ml of tetrahydrofuran. 34 μl of 2-methylpyrrolidine and 18 μl of glacial acetic acid are added, and the mixture is stirred at 60° C. for 6 h. After cooling to 25° C., 103 mg of sodium triacetoxyborohydride are added and stirred at 25° C. for a further 12 h. The mixture is poured into water, extracted three times with dichloromethane, and the combined organic phases are dried over sodium sulfate. After filtration, the filtrate is evaporated to dryness and purified by chromatography (reversed phase HPLC).

Workup

  1. temperatureAfter cooling to 25° C.
  2. stirringstirred at 25° C. for a further 12 h
  3. extractionextracted three times with dichloromethane
  4. dry with materialthe combined organic phases are dried over sodium sulfate
  5. filtrationAfter filtration
  6. customthe filtrate is evaporated to dryness
  7. custompurified by chromatography (reversed phase HPLC)

Sources & evidence

ORD record
ord-bbbd46ebdf8e40be93b2b1d9628ccaf4
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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