Diisopropylethylamine → (3-Nitro-pyridin-4-yl)-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-amine

HRID 273044Notes

Reaction equation

HRID 273044 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Cl.C(O[C:37]1[CH:42]=[CH:41][N:40]=[CH:39][C:38]=1[N+:43]([O-:45])=[O:44])C>C(#N)C>[N+:43]([C:38]1[CH:39]=[N:40][CH:41]=[CH:42][C:37]=1[NH:23][CH2:22][C:16]1([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:11][CH:12]=2)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1)([O-:45])=[O:44]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamineHCID 124074974-Ethoxy-3-nitropyridine hydrochloride2×

Product 1

HCID 68578716(3-Nitro-pyridin-4-yl)-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-amineYield 38.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of {4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (390 mg, 1.2 mmol) in acetonitrile (˜5 mL), was added Hunig's base (230 μL, 1.35 mmol, 1.1 eq.) and 4-ethoxy-3-nitropyridine hydrogen chloride (250 mg, 1.2 mmol, 1 eq.) and the mixture stirred at reflux for 72 hours. To this a further portion of 4-ethoxy-3-nitropyridine hydrogen chloride (50 mg, 0.24 mmol, 0.2 eq.) was added and the mixture stirred at reflux for a further 24 hours. The reaction mixture was then concentrated in vacuo to give a dark yellow oily residue. This was partitioned between 2M NaOH (30 mL) and DCM (2×30 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to give a dark yellow oil. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:0.2 to 90:10:1, by volume) to provide the title compound (205 mg, 38%). HRMS ESI+ m/z 441.2486 [MH]+.

Workup

  1. temperatureat reflux for 72 hours
  2. stirringthe mixture stirred
  3. temperatureat reflux for a further 24 hours
  4. concentrationThe reaction mixture was then concentrated in vacuo
  5. customto give a dark yellow oily residue
  6. customThis was partitioned between 2M NaOH (30 mL) and DCM (2×30 mL)
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a dark yellow oil
  11. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:0.2 to 90:10:1, by volume)

Sources & evidence

ORD record
ord-865cdabff8db467b81002bb1b7d9af99
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…