1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 136342067, compound

HRID 1726085Notes

Reaction equation

HRID 1726085 reaction equation
N12CCCN=C1CCCCC2.[N:12]1([CH2:18][CH2:19][O:20][C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[NH:26][C:25]([C:30]2[C:38]4[C:33](=[CH:34][CH:35]=[C:36](O)[CH:37]=4)[NH:32][N:31]=2)=[CH:24]3)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.[N+](C1C=C[C:46]([O:49][P:50](C)(=[O:61])[O:51]C2C=CC([N+]([O-])=O)=CC=2)=CC=1)([O-])=O.C(=O)(O)[O-].[Na+]>ClCCl.CO>[CH3:46][O:49][P:50]([C:36]1[CH:37]=[C:38]2[C:33](=[CH:34][CH:35]=1)[NH:32][N:31]=[C:30]2[C:25]1[NH:26][C:27]2[C:23]([CH:24]=1)=[CH:22][C:21]([O:20][CH2:19][CH2:18][N:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[CH:29][CH:28]=2)(=[O:51])[OH:61]

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 98876Bis(4-nitrophenyl) methylphosphonateHCID 516892Sodium BicarbonateHCID 136055975HCID 136055975, compound

Product 1

HCID 136342067HCID 136342067, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

77 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a solution of 193 mg of 3-[5-(2-piperidin-1-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-ol and 173.5 mg of methylphosphonic acid bis-(4-nitrophenyl) ester in 10 ml of dichloromethane and the mixture is allowed to react at 20° C. After reaction for three hours, 300 μl of methanol and then 77 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene are added and the reaction is continued at 20° C. for 16 hours. The reaction medium is then taken up in a mixture of dichloromethane (150 ml) and a saturated sodium bicarbonate solution (100 ml). After separation by settling out and extraction with dichloromethane (50 ml), the organic extracts are combined, dried over magnesium sulfate and then evaporated under reduced pressure. The crude compound thus obtained is purified by chromatography on silica (Interchrom column, reference DC0210, 20 g silica, eluent dichloromethane/methanol 9/1 v/v, 15 ml/min). The fractions containing the expected compound are combined and evaporated under reduced pressure. 89 mg of 3-[5-(2-piperidin-1-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-ylphosphonic acid methyl ester are isolated and characterized.

Workup

  1. customto react at 20° C
  2. customAfter reaction for three hours
  3. customAfter separation
  4. extractionextraction with dichloromethane (50 ml)
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe crude compound thus obtained
  8. customis purified by chromatography on silica (Interchrom column, reference DC0210, 20 g silica, eluent dichloromethane/methanol 9/1 v/v, 15 ml/min)
  9. additionThe fractions containing the expected compound
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2ff50b034c664745a49163632dd68f67
Source dataset
uspto-grants-2009_02
Patent number
US07491710B2

Reaction notes

Loading…