Hydrochloric Acid → HCID 66837688, compound

HRID 1631176Notes

Reaction equation

HRID 1631176 reaction equation
[C:1](N1C=CN=C1)([N:3]1[CH:7]=[CH:6][N:5]=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.C(NCCN)(OC(C)(C)C)=O.Cl.C(=O)(O)[O-]>N1C=CC=CC=1>[NH2:5][CH2:6][CH2:7][NH:3][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]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 769Bicarbonate IonHCID 682631,1'-CarbonyldiimidazoleHCID 187201N-BOC-ethylenediamineHCID 56943446[2-Amino-6-[4,5-difluoro-2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

Product 1

HCID 66837688HCID 66837688, 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 N-Boc-ethylenediamine 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 and stirred at 25° C. for 3 h, 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. stirringstirred at 25° C. for 3 h
  4. washwashed 3 times with 150 ml of dichloromethane each time
  5. washThe organic phases are washed twice with 50 ml of water each time
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness in vacuo
  9. dissolutionThe residue is dissolved in 1 ml of dimethyl sulfoxide
  10. custompurified by chromatography (reversed phase)

Sources & evidence

ORD record
ord-56a66dadfcb544e2b5102f1f652f0410
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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