2-Chloro-3-nitropyridine → (3-Nitro-pyridin-2-yl)-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-amine

HRID 273045Notes

Reaction equation

HRID 273045 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:34]1[C:39]([N+:40]([O-:42])=[O:41])=[CH:38][CH:37]=[CH:36][N:35]=1>C(#N)C>[N+:40]([C:39]1[C:34]([NH:23][CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[N:35][CH:36]=[CH:37][CH:38]=1)([O-:42])=[O:41]

Participants

5

Reactant 3

HCID 796132-Chloro-3-nitropyridineHCID 81531DiisopropylethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 68578573(3-Nitro-pyridin-2-yl)-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-amineYield 107.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of {4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (320 mg, 1.0 mmol) in acetonitrile (˜5 mL), was added Hunig's base (190 μL, 1.1 mmol, 1.1 eq.) and 2-chloro-3-nitropyridine (175 mg, 1.1 mmol, 1.1 eq.) and the mixture stirred at reflux for 4 hours. The reaction mixture was then concentrated in vacuo and partitioned between saturated NaHCO3 solution (20 mL) and DCM (2×20 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to give the title compound (475 mg, 100%) as a yellow oil. LRMS APCI+ m/z 441 [MH]+.

Workup

  1. temperatureat reflux for 4 hours
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. custompartitioned between saturated NaHCO3 solution (20 mL) and DCM (2×20 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a5d8625d38514ec3bcbd2fba8ea5080b
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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