Hydrochloric Acid → HCID 20605627, compound

HRID 481066Notes

Reaction equation

HRID 481066 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:9]2[C:10]([NH:14][CH2:15][CH:16](OC)OC)=[N:11][CH2:12][CH2:13][C:8]=2[N:7]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)[CH:6]=1)=[O:4].Cl.C([O-])([O-])=O.[K+].[K+]>CO.ClCCl>[CH3:1][O:2][C:3]([C:5]1[C:9]2[C:10]3[N:11]([CH:16]=[CH:15][N:14]=3)[CH2:12][CH2:13][C:8]=2[N:7]([CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)[CH:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 20605658HCID 20605658, compound

Product 1

HCID 20605627HCID 20605627, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
63 °C

Procedure

To a solution of 4-(2,2-Dimethoxy-ethylamino)-1-[2-(4-nitro-phenyl)-ethyl]-6,7-dihydro-1H-pyrrolo[3,2-c]pyridine-3-carboxylic acid methyl ester (25.33 mmol) in 125 mL MeOH is 10 mL HCl conc. added. It is heated at 63° C. for 15 hours. Since the reaction is not complete another 5 mL HCl conc. is added, and it is heated again at 63° C. for 10 hours. The solvent is evaporated in vacuo, and the remaining oil is dissolved in MeOH whereby K2CO3 (1.2 eq.) is added. After stirred at RT for 1 h the solid is filtered off, washed with MeOH and the filtrate is evaporated in vacuo yielding a yellow solid that is protonated. The protonated product is stirred in Dichloromethane and saturated NaCO3 sol. until everything dissolved. The two layers are separated and the water layer is extracted two times with dichloromethane. The organic layers are collected, dried and evaporated in vacuo yielding a free base which is triturated in ethyl acetate yielding 6-[2-(4-Nitro-phenyl)-ethyl]-5,6-dihydro-4H-1,3a,6-triaza-as-indacene-8-carboxylic acid methyl ester, 9.11 g, as a yellow solid (77%): 1H NMR (CD3OD) 2.76 (t, 2H), 3.18 (t, 2H), 3.78 (s, 3H), 4.07 (t, 2H), 4.28 (t, 2H), 6.94 (s, 1H), 7.01 (s, 1H), 7.31 (d, 3H), 8.10 (d, 2H); LRMS calcd 366.38, found [M+H] 367.2.

Workup

  1. additionis added
  2. temperatureit is heated again at 63° C. for 10 hours
  3. customThe solvent is evaporated in vacuo
  4. additionis added
  5. filtrationis filtered off
  6. washwashed with MeOH
  7. customthe filtrate is evaporated in vacuo
  8. customyielding a yellow solid
  9. customThe two layers are separated
  10. extractionthe water layer is extracted two times with dichloromethane
  11. customThe organic layers are collected
  12. customdried
  13. customevaporated in vacuo
  14. customyielding a free base which
  15. customis triturated in ethyl acetate

Sources & evidence

ORD record
ord-77a77cd59c4143e4b95da61141980a9c
Source dataset
uspto-grants-2003_11
Patent number
US06653471B2

Reaction notes

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