1-Methylpiperazine → Tert-butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

HRID 1253678Notes

Reaction equation

HRID 1253678 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][C:44]2([CH2:51][CH2:50][CH:49]([C:52]([OH:54])=O)[CH2:48][CH2:47]2)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].[CH3:55][N:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1.C(N(C(C)C)C(C)C)C>O1CCCC1>[CH3:55][N:56]1[CH2:61][CH2:60][N:59]([C:52]([CH:49]2[CH2:48][CH2:47][C:44]3([CH2:43][CH2:42][N:41]([C:39]([O:38][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:40])[CH2:46][CH2:45]3)[CH2:51][CH2:50]2)=[O:54])[CH2:58][CH2:57]1

Participants

7

Reactant 5

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 152287053-(tert-Butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid

Product 1

HCID 67546380Tert-butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.32 g, 1 eq.) and 1-hydroxybenzotriazole hydrate (0.14 g, 1 eq.) were added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.3 g, 1 eq.) in tetrahydrofuran (20 ml) and the reaction mixture was stirred at room temperature for 0.5 h. 1-Methylpiperazine (0.11 ml, 1 eq.) and N-ethyl-diisopropylamine (0.17 ml, 1 eq.) were then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was concentrated, methylene chloride and sat. NaHCO3 solution were added to the residue and the aqueous phase was extracted with methylene chloride a further 2×. The combined organic phases were washed 1× with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) 10:1:0.05) in order to obtain the desired product (AMN-10). Yield: 0.22 g (101%)

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additionmethylene chloride and sat. NaHCO3 solution were added to the residue
  3. extractionthe aqueous phase was extracted with methylene chloride a further 2×
  4. washThe combined organic phases were washed 1× with sat. NaCl solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) 10:1:0.05) in order

Sources & evidence

ORD record
ord-82a34fe68c6e442ca1849b6deddd21de
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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