1,2-Dichloroethane → Cyclopropanesulfonic acid {17-[2-(4-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carbonyl}-amide

HRID 1443501Notes

Reaction equation

HRID 1443501 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]([O:18][CH:19]3[CH2:36][CH:35]4[N:21]([C:22](=[O:42])[N:23]([CH3:41])[CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH:30]5[C:32]([C:38](O)=[O:39])([NH:33][C:34]4=[O:37])[CH2:31]5)[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:45])[C:12]([O:43][CH3:44])=[CH:13][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.C(Cl)CCl.[CH:50]1([S:53]([NH2:56])(=[O:55])=[O:54])[CH2:52][CH2:51]1.C1CCN2C(=NCCC2)CC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:16]([O:18][CH:19]3[CH2:36][CH:35]4[N:21]([C:22](=[O:42])[N:23]([CH3:41])[CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH:30]5[C:32]([C:38]([NH:56][S:53]([CH:50]6[CH2:52][CH2:51]6)(=[O:55])=[O:54])=[O:39])([NH:33][C:34]4=[O:37])[CH2:31]5)[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:45])[C:12]([O:43][CH3:44])=[CH:13][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 311Citric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 6841134017-[2-(4-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acid

Product 1

HCID 73436956Cyclopropanesulfonic acid {17-[2-(4-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carbonyl}-amideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the acid (153) (92 mg, 0.15 mmol) and EDC (38 mg, 0.2 mmol) in dry DCM (2 ml) was stirred at room temperature overnight. Cyclopropylsulfonamide (48 mg, 0.4 mmol) and DBU (76 mg, 0.5 mmol) was added and the mixture was stirred at room temperature for 6 hours. 5% Citric acid was added and the mixture was extracted three times with ethyl acetate. The organic phase was washed with 5% citric acid and brine, dried with sodium sulphate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with ether-methanol which gave the title compound (70 mg, 65%), MS (M+H) 720.

Workup

  1. extractionthe mixture was extracted three times with ethyl acetate
  2. washThe organic phase was washed with 5% citric acid and brine
  3. dry with materialdried with sodium sulphate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluted with ether-methanol which

Sources & evidence

ORD record
ord-c85433d840e542d0a90671b458b5c1bd
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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