Dichloromethane → HCID 21701558, compound

HRID 1596289Notes

Reaction equation

HRID 1596289 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Br:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([OH:31])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:55][CH2:56][N:57]1[CH2:62][CH2:61][N:60]([CH3:63])[CH2:59][CH2:58]1.C(Cl)[Cl:65]>>[ClH:65].[Br:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH2:55][CH2:56][N:57]4[CH2:62][CH2:61][N:60]([CH3:63])[CH2:59][CH2:58]4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 21701558HCID 21701558, compoundYield 41%

Procedure

Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a suspension of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (146 mg, 0.4 mmol), triphenylphosphine (314 mg, 1.2 mmol) and 1-(2-hydroxyethyl)4-methylpiperazine (86 mg, 0.6 mmol), (prepared as described for the starting material in Example 17), in methylene chloride (5 ml). The mixture was stirred for 1 hour at ambient temperature and the mixture was purified by column chrormatography eluting with methylene chloride/methanol (90/10 followed by 80/20). The purified product was triturated with ether, collected by filtration and dried under vacuum. The solid was dissolved in methylene chloride and 3M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the resulting oil was triturated with ether. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline hydrochloride (100 mg, 41%).

Workup

  1. custom(prepared
  2. customthe mixture was purified by column chrormatography
  3. washeluting with methylene chloride/methanol (90/10 followed by 80/20)
  4. customThe purified product was triturated with ether
  5. filtrationcollected by filtration
  6. customdried under vacuum
  7. dissolutionThe solid was dissolved in methylene chloride
  8. addition3M ethereal hydrogen chloride (0.5 ml) was added
  9. customThe volatiles were removed by evaporation
  10. customthe resulting oil was triturated with ether
  11. filtrationThe solid was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-af5079b0452e44c8a05ac1f9ba333cec
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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