Methanol → methylphosphonic acid methyl ester 3-[5-(2-morpholin-4-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester

HRID 1726101Notes

Reaction equation

HRID 1726101 reaction equation
[N+](C1C=C[C:7]([O:10][P:11]([CH3:23])(=[O:22])[O:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=2)=CC=1)([O-])=O.[N:24]1([CH2:30][CH2:31][O:32][C:33]2[CH:34]=[C:35]3[C:39](=[CH:40][CH:41]=2)[NH:38][C:37]([C:42]2C4C(=CC=C(O)C=4)N[N:43]=2)=[CH:36]3)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C1CCN2C(=NCCC2)CC1.CO>ClCCl>[N:24]1([CH2:30][CH2:31][O:32][C:33]2[CH:34]=[C:35]3[C:39](=[CH:40][CH:41]=2)[NH:38][C:37]([C:42]2[C:15]4[C:16](=[CH:17][CH:18]=[C:13]([O:12][P:11]([CH3:23])(=[O:22])[O:10][CH3:7])[CH:14]=4)[NH:19][N:43]=2)=[CH:36]3)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 887MethanolHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 98876Bis(4-nitrophenyl) methylphosphonateHCID 1360560083-[5-(2-morpholin-4-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-ol

Product 1

HCID 136055969methylphosphonic acid methyl ester 3-[5-(2-morpholin-4-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 170 mg of methylphosphonic acid bis-(4-nitrophenyl)ester (prepared according to procedure E) and 189.7 mg of 3-[5-(2-morpholin-4-yl-ethoxy)-1H-indol-2-yl]-1H-indazol-5-ol in 17 ml of dichloromethane (stabilized with amylene) is stirred at ambient temperature. A solution of 75 μl of DBU in 500 μl of dichloromethane is added dropwise over 10 minutes. Stirring is maintained overnight. 204 μl of methanol are added with 75 μl of DBU. The solution is stirred for 24 hours. The reaction medium is concentrated under vacuum and the crude is then taken up with 25 ml of ethyl acetate and washed with 4 times 25 ml of distilled water. The organic phase is dried over magnesium sulfate, filtered and concentrated under vacuum. The reaction crude is purified by flash chromatography on 5 g of 40-63 μm silica. Eluents: 98/2 then 95/5 dichloromethane/methanol. 95 mg of methylphosphonic acid methyl ester 3-[5-(2-morpholin-4-yl-ethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester are collected.

Workup

  1. stirringStirring
  2. temperatureis maintained overnight
  3. stirringThe solution is stirred for 24 hours
  4. concentrationThe reaction medium is concentrated under vacuum
  5. washwashed with 4 times 25 ml of distilled water
  6. dry with materialThe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe reaction crude
  10. customis purified by flash chromatography on 5 g of 40-63 μm silica
  11. custom95 mg of methylphosphonic acid methyl ester 3-[5-(2-morpholin-4-yl-ethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester are collected

Sources & evidence

ORD record
ord-d0be5ecf1d3a4cfb93452b0066af8f0c
Source dataset
uspto-grants-2009_02
Patent number
US07491710B2

Reaction notes

Loading…