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Hydrochloric Acid → 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (2-dimethylaminoethyl)carbamate

HRID 1631174
Notes
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Reaction equation

HRID 1631174 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[N:23]=[C:22]([C:24]([N:26]2[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:35]3[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=3[CH2:43][OH:44])[CH:20]=2)[N:15]=1.[CH3:45]N(C)CCN.Cl.C(=O)(O)[O-]>N1C=CC=CC=1>[CH3:45][N:10]([CH3:9])[CH2:11][CH2:12][NH:8][C:1](=[O:2])[O:44][CH2:43][C:36]1[CH:37]=[C:38]([F:42])[C:39]([F:41])=[CH:40][C:35]=1[C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([NH2:13])[N:23]=[C:22]2[C:24]([N:26]1[CH2:27][C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:34]1)=[O:25]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 769Bicarbonate IonHCID 66053N,N-DimethylethylenediamineHCID 682631,1'-CarbonyldiimidazoleHCID 56943446[2-Amino-6-[4,5-difluoro-2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

Product 1

HCID 56944456
2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (2-dimethylaminoethyl)carbamate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
0 °C

Procedure

400 mg of 1,1′-carbonyldiimidazole are dissolved in 10 ml of pyridine and cooled to 0° C. A solution of 1.0 g of [2-amino-6-(4,5-difluoro-2-hydroxymethylphenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone dissolved in 10 ml of pyridine is added. The mixture is subsequently stirred at 0° C. for 2 h and at 25° C. for 2 h. 300 μl of N,N-dimethylethylenediamine are then added, and the mixture is stirred at 25° C. for a further 18 h. The mixture is added to 250 ml of 1 N HCl, neutralised using bicarbonate solution and washed 3 times with 150 ml of dichloromethane each time. The organic phases are washed twice with 50 ml of water each time, dried over sodium sulfate, filtered and evaporated to dryness in vacuo. The residue is dissolved in 1 ml of dimethyl sulfoxide and purified by chromatography (reversed phase).

Workup

  1. additionis added
  2. stirringthe mixture is stirred at 25° C. for a further 18 h
  3. washwashed 3 times with 150 ml of dichloromethane each time
  4. washThe organic phases are washed twice with 50 ml of water each time
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. dissolutionThe residue is dissolved in 1 ml of dimethyl sulfoxide
  9. custompurified by chromatography (reversed phase)

Sources & evidence

ORD record
ord-1161e325794642478c22d1d764aef42e
Source dataset
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08791129B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes