Hydrochloric Acid → N-(3,4-Dichlorophenyl)-3-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7-dihydroisoxazolo[4,5-c]pyridine-5(4H)-carboxamide

HRID 1808385Notes

Reaction equation

HRID 1808385 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][C:12]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.CN1CCOCC1.[Cl:34][C:35]1[CH:36]=[C:37]([NH:42][C:43]([N:45]2[CH2:50][CH2:49][C:48]3[O:51][N:52]=[C:53]([C:54](O)=[O:55])[C:47]=3[CH2:46]2)=[O:44])[CH:38]=[CH:39][C:40]=1[Cl:41].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.C(OCC)C>CN(C=O)C>[Cl:34][C:35]1[CH:36]=[C:37]([NH:42][C:43]([N:45]2[CH2:50][CH2:49][C:48]3[O:51][N:52]=[C:53]([C:54]([N:17]4[CH2:18][CH2:19][C:12]5([CH2:13][CH2:14][N:9]([C:6]6[CH:5]=[CH:4][N:3]=[CH:8][CH:7]=6)[CH2:10][CH2:11]5)[CH2:15][CH2:16]4)=[O:55])[C:47]=3[CH2:46]2)=[O:44])[CH:38]=[CH:39][C:40]=1[Cl:41]

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59483858HCID 59483858, compoundHCID 66701057HCID 66701057, compound

Product 1

HCID 59483817N-(3,4-Dichlorophenyl)-3-(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7-dihydroisoxazolo[4,5-c]pyridine-5(4H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecane dihydrochloride (0.17 g, 0.562 mmol) was dissolved in DMF (8.6 ml) and triethylamine (0.15 ml, 1.123 mmol), and 4-methylmorpholine (0.17 g, 1.685 mmol) was added, followed by 5-(3,4-dichlorophenylcarbamoyl)-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-carboxylic acid (0.2 g, 0.562 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.32 g, 1.3 mmol). The reaction mixture was stirred for 15 h at RT, and then the solvent was removed in vacuo. The residue was taken up in ethyl acetate and sat. sodium hydrogen carbonate solution, and the phases were separated. The aqueous phase was extracted with ethyl acetate, and then the combined organic phases were washed with sat. sodium chloride solution and sat. sodium hydrogen carbonate solution, dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol 20:1+1% ammonia solution (25% aq.)). The purified product was dissolved in methyl ethyl ketone (2 ml); 2 M hydrogen chloride in diethyl ether (4 equiv.) was added at 0° C., and stirring was carried out for 1 h in an ice bath. The solid was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.16 g (47%). MS, Rt=3.4 min; m/z=569.3 [MH]+

Workup

  1. customthe solvent was removed in vacuo
  2. customsat. sodium hydrogen carbonate solution, and the phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe combined organic phases were washed with sat. sodium chloride solution and sat. sodium hydrogen carbonate solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/methanol 20:1+1% ammonia solution (25% aq.))
  8. dissolutionThe purified product was dissolved in methyl ethyl ketone (2 ml)
  9. stirringstirring
  10. waitwas carried out for 1 h in an ice bath
  11. filtrationThe solid was filtered out with suction
  12. washwashed with diethyl ether
  13. customdried in vacuo

Sources & evidence

ORD record
ord-7c12467c9dc544e9b91dbcccdf46398b
Source dataset
uspto-grants-2013_01
Patent number
US08357717B2

Reaction notes

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