Acetic Acid → [2-Amino-6-(2-{[ethyl-(2-hydroxyethyl)amino]methyl}-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

HRID 1631116Notes

Reaction equation

HRID 1631116 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]=[C:29]([F:31])[CH:28]=[CH:27][C:24]=3C=O)[CH:8]=2)[N:3]=1.[CH2:32]([NH:34][CH2:35][CH2:36][OH:37])[CH3:33].[C:38](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]=[C:29]([F:31])[CH:28]=[CH:27][C:24]=3[CH2:38][N:34]([CH2:32][CH3:33])[CH2:35][CH2:36][OH:37])[CH:8]=2)[N:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 80722-(Ethylamino)ethanolHCID 5049666Sodium triacetoxyborohydrideHCID 867625702-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-4-fluorobenzaldehyde

Product 1

HCID 56943510[2-Amino-6-(2-{[ethyl-(2-hydroxyethyl)amino]methyl}-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

114 mg of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4-fluorobenzaldehyde are dissolved in 2 ml of 1,2-dichloroethane and 2 ml of tetrahydrofuran. 57 μl of 2-(ethylamino)ethanol and 28 μl of glacial acetic acid are added, and the mixture is stirred at 60° C. for 6 h. After cooling to 25° C., 216 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-c5e0121f0a0d472696b2999c890fd511
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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