1,1'-Carbonyldiimidazole → N-[17-[2-(3-isopropylpyrazol-1-yl)-7-methoxy-8-methylquinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclo-propyl)sulfonamide

HRID 1443497Notes

Reaction equation

HRID 1443497 reaction equation
[CH:1]([C:4]1[CH:8]=[CH:7][N:6]([C:9]2[N:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39](O)=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:46])[C:13]([O:44][CH3:45])=[CH:14][CH:15]=3)[N:10]=2)[N:5]=1)([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:59]1([S:62]([NH2:65])(=[O:64])=[O:63])[CH2:61][CH2:60]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[CH:1]([C:4]1[CH:8]=[CH:7][N:6]([C:9]2[N:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:65][S:62]([CH:59]6[CH2:61][CH2:60]6)(=[O:64])=[O:63])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:46])[C:13]([O:44][CH3:45])=[CH:14][CH:15]=3)[N:10]=2)[N:5]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 6868954017-[2-(3-Isopropylpyrazol-1-yl)-7-methoxy-8-methylquinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

Product 1

HCID 76593261N-[17-[2-(3-isopropylpyrazol-1-yl)-7-methoxy-8-methylquinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclo-propyl)sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the acid (146) (53 mg, 0.084 mmol), and carbonyldiimidazole (29.4 mg, 0.181 mmol) in dry THF (10 mL) was stirred at reflux under nitrogen for 2 h. The reaction mixture was cooled to room temperature and cyclopropylsulfonamide (50.3 mg, 0.415 mmol) and DBU (34.1 mg, 0.224 mmol) were added. This solution was heated at 50° C. for 15 h. Then, the reaction mixture was cooled down at room temperature and concentrated under reduced pressure. The residue was partitioned between AcOEt and diluted HCl, the organic layer was washed with brine, dried (Na2SO4) and evaporated. Purification by flash chromatography (EtOAc/CH2Cl2, 2:8) provided the desired product which was subsequently dissolved in a minimum of ethanol and diluted with water. Filtration of the precipitate afforded the title compound (14.8 mg, 24%) as a white powder, m/z=734 (M+H)+.

Workup

  1. temperatureat reflux under nitrogen for 2 h
  2. temperatureThis solution was heated at 50° C. for 15 h
  3. temperatureThen, the reaction mixture was cooled down at room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between AcOEt and diluted HCl
  6. washthe organic layer was washed with brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customPurification by flash chromatography (EtOAc/CH2Cl2, 2:8)

Sources & evidence

ORD record
ord-c63ee7b73b0046c399f98b4040d2b20d
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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