Hydrochloric Acid → HCID 66836705, compound

HRID 1631177Notes

Reaction equation

HRID 1631177 reaction equation
[C:1](N1C=CN=C1)(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.O[CH2:46][CH2:47][NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52].N12CCCN=C1CCCCC2.Cl.C(=O)(O)[O-]>N1C=CC=CC=1>[C:51]([O:50][C:49]([NH:48][CH2:47][CH2:46][C:1]([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])=[O:2])=[O:55])([CH3:54])([CH3:53])[CH3:52]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 769Bicarbonate IonHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 56943446[2-Amino-6-[4,5-difluoro-2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

Product 1

HCID 66836705HCID 66836705, compound

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. 400 mg of tert-butyl N-(2-hydroxyethyl)carbamate and 400 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene 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-33ec40c842424574aaabdc23d8c01b92
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

Loading…