Tris(hydroxymethyl)aminomethane → HCID 12043808, compound

HRID 1282021Notes

Reaction equation

HRID 1282021 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:19])[C:16]([OH:18])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.[C:24]([O:28][C:29]([N:31]1[C:35]([NH2:36])=[CH:34][C:33]([CH:37]2[CH2:39][CH2:38]2)=[N:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(O)C(N)(CO)CO>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([CH3:19])[C:16]([NH:36][C:35]2[N:31]([C:29]([O:28][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:30])[N:32]=[C:33]([CH:37]3[CH2:39][CH2:38]3)[CH:34]=2)=[O:18])=[CH:13][CH:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 24386Thionyl ChlorideHCID 3780288HCID 3780288, compoundHCID 11356513tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate

Product 1

HCID 12043808HCID 12043808, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

265 mg (1 mmol) of 2-{4-[(tert-butoxycarbonyl)amino]phenyl}propanoic acid were treated at 4° C. under nitrogen with 146 μl (2 mmol) of thionylchloride. The reaction mixture was stirred for 2.5 hours and the temperature was gradually raised to room temperature. The mixture was taken up with tetrahydrofuran and evaporated thoroughly. The resulting acyl chloride, without any further purification, was dissolved in 3 ml of dry tetrahydrofuran and added dropwise to a solution of 178 mg (0.8 mmol) of tert-butyl-5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate in 3 ml of tetrahydrofuran. 312 mg (1 mmol, loading 3.2 mmol/g) of polymer supported triethylamine were then added under stirring. After 2.5 hours 80 mg (loading 3.2 mmol/g) of polymer supported trisamine were finally added in order to quench the excess of acyl chloride. After 2 hours, the resins were filtered and washed with methanol and dichloromethane. Evaporation of the filtrate afforded 263 mg of the title compound as a foam (70% yield).

Workup

  1. customevaporated thoroughly
  2. customThe resulting acyl chloride, without any further purification
  3. dissolutionwas dissolved in 3 ml of dry tetrahydrofuran
  4. additionwere then added
  5. stirringunder stirring
  6. waitAfter 2.5 hours 80 mg (loading 3.2 mmol/g) of polymer supported
  7. customto quench the excess of acyl chloride
  8. waitAfter 2 hours
  9. filtrationthe resins were filtered
  10. washwashed with methanol and dichloromethane
  11. customEvaporation of the filtrate

Sources & evidence

ORD record
ord-abb4b32e56e847f086e76a7364723d08
Source dataset
uspto-grants-2002_09
Patent number
US06455559B1

Reaction notes

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