Diazald → HCID 71112438, compound

HRID 1775503Notes

Reaction equation

HRID 1775503 reaction equation
[OH-].[K+].CN(N=O)S(C1C=CC(C)=CC=1)(=O)=O.[N+:17](=[CH2:19])=[N-].CCOCC.[CH3:25][C:26]1([CH3:49])[CH2:39][N:38]2[C:29](=[N:30][C:31]3[C:36]([C:37]2=[O:40])=[CH:35][CH:34]=[C:33]([CH:41]=[CH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45]N=2)[CH:32]=3)[CH2:28][CH2:27]1.[N+](=C)=[N-]>O.C(O)C.CCOCC.C(Cl)Cl>[CH3:49][C:26]1([CH3:25])[CH2:39][N:38]2[C:29](=[N:30][C:31]3[C:36]([C:37]2=[O:40])=[CH:35][CH:34]=[C:33]([CH:41]2[CH2:42][CH:43]2[C:48]2[CH:47]=[CH:46][CH:45]=[CH:19][N:17]=2)[CH:32]=3)[CH2:28][CH2:27]1

Participants

10

Reactant 5

HCID 6628DiazaldHCID 9550DiazomethaneHCID 14797Potassium HydroxideHCID 21186548Diazomethane diethyletherHCID 68001294HCID 68001294, compound

Product 1

HCID 71112438HCID 71112438, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of KOH (119 equiv) in H2O and ethanol heated to 65° C. was added N-methyl-N-nitroso-p-toluenesul-fonamide (3 equiv) in ether. The diazomethane ether solution was distillated and collected at −78° C. Then, a solution of vinyl-containing material (e.g., 8,8-dimethyl-3-(2-(pyridin-2-yl)vinyl)-8,9-dihydro-6H-pyrido[2,1-b]-quinazolin-11(7H)-one, 1 equiv) and Rh(OAc)2(0.1 equiv) in CH2Cl2 was added to the ethereal diazomethane solution and stirred overnight at room temperature. The mixture was quenched with 10% acetic acid in ethyl acetate, diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography (EtOAc:n-hexane=1:3) to give the cyclopropanated product (e.g., 8,8-dimethyl-3-(2-(pyridin-2-yl)cyclopropyl)-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one).

Workup

  1. customcollected at −78° C
  2. customThe mixture was quenched with 10% acetic acid in ethyl acetate
  3. additiondiluted with H2O
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by column chromatography (EtOAc:n-hexane=1:3)

Sources & evidence

ORD record
ord-9db52702a019494eb8fa406ae9f38f64
Source dataset
uspto-grants-2016_02
Patent number
US09260452B2

Reaction notes

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