Hydrochloric Acid → 1,3-dimethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]dihydrochloride

HRID 1908011Notes

Reaction equation

HRID 1908011 reaction equation
[C:1]([CH:4]1[C:13]2([CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)[O:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=O)(=O)[CH3:2].[NH2:27][N:28](C)[C:29](=O)OC(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.NN(C)C(=O)OCCCC.[ClH:59]>C(O)C>[ClH:59].[ClH:59].[CH3:29][N:28]1[C:5]2[C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[O:12][C:13]3([CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)[C:4]=2[C:1]([CH3:2])=[N:27]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 521998p-Toluenesulfonic acid monohydrateHCID 37482801-Boc-1-methylhydrazine2×HCID 20464644HCID 20464644, compoundHCID 58551325Tert-butyl 3-acetyl-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 674668861,3-dimethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]dihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3-acetyl-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (250 mg, 0.70 mmol), tert-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) and p-toluene sulfonic acid monohydrate (27 mg, 0.14 mmol) in ethanol (8 mL) was heated at 80° C. overnight. Additional tert-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) was added and the mixture was heated at 80° C. for 6.5 h, then another portion of ten-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) was added and the mixture was heated at 80° C. for 2 h. HCl (0.87 mL of 4.0 M in dioxane, 3.5 mmol) was added and the mixture was stirred at 80° C. for 1 h. After cooling, the precipitate was collected via filtration and washed with cold EtOH to provide 1,3-dimethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]dihydrochloride (295 mg, >100%, may contain some methyl hydrazine HCl salt) as a solid. ESI-MS m/z calc. 269.2. found 270.5 (M+1)+; Retention time: 1.11 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.71 (dd, J=7.8, 1.3 Hz, 1H), 7.33-7.27 (m, 1H), 7.17-7.14 (m, 1H), 7.11-7.05 (m, 1H), 4.02 (s, 3H), 3.28-3.15 (m, 4H), 2.40-2.30 (m, 2H), 2.23 (s, 3H), 2.07-1.97 (m 2H).

Workup

  1. temperaturethe mixture was heated at 80° C. for 6.5 h
  2. temperaturethe mixture was heated at 80° C. for 2 h
  3. temperatureAfter cooling
  4. filtrationthe precipitate was collected via filtration
  5. washwashed with cold EtOH

Sources & evidence

ORD record
ord-8bdebc307ff64b38bd65422979663fbe
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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