Dichloromethane → 4-(4-Bromo-2-fluoroanilino)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline hydrochloride

HRID 547232Notes

Reaction equation

HRID 547232 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:54]=[S:55]1(=[O:65])[CH2:60][CH2:59][N:58]([CH2:61][CH2:62][CH2:63]O)[CH2:57][CH2:56]1.C(Cl)[Cl:67]>>[ClH:67].[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][CH2:63][CH2:62][CH2:61][N:58]4[CH2:57][CH2:56][S:55](=[O:65])(=[O:54])[CH2:60][CH2:59]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 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 114354734-(3-Hydroxypropyl)thiomorpholine 1,1-Dioxide2×HCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 670451524-(4-Bromo-2-fluoroanilino)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline hydrochlorideYield 47%

Procedure

Diethyl azodicarboxylate (220 μl, 1.4 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (170 mg, 0.46 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (367 mg, 1.4 mmol) and 3-(1,1-dioxothiomorpholino)-1-propanol (135 mg, 0.7 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature and further triphenylphosphine (61 mg, 0.23 mmol), 3-(1,1-dioxothiomorpholino)-1-propanol (30 mg, 0.23 mmol) and diethyl azodicarboxylate (37 μl, 0.23 mmol) were added. The mixture was stirred for 1 hour at ambient temperature and the mixture was purified by pouring it on to a column of silica and eluting with methylene chloride/methanol (95/5). The purified product was dissolved in methylene chloride/methanol, 2.2M ethereal hydrogen chloride (1 ml) was added and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline hydrochloride (138 mg, 47%).

Workup

  1. custom(prepared
  2. stirringThe mixture was stirred for 1 hour at ambient temperature
  3. customthe mixture was purified
  4. additionby pouring it on to a column of silica
  5. washeluting with methylene chloride/methanol (95/5)
  6. dissolutionThe purified product was dissolved in methylene chloride/methanol
  7. addition2.2M ethereal hydrogen chloride (1 ml) was added
  8. customthe volatiles were removed by evaporation
  9. customThe residue was triturated with ether
  10. filtrationcollected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-1911cdf7bac34bf0b8103c5d8e2c3d1e
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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