Tris(hydroxymethyl)aminomethane → Hydrochloric Acid

HRID 1873984Notes

Reaction equation

HRID 1873984 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@@H:9]([O:39][Si](CC)(CC)CC)[CH2:10][N:11](C(OC(C)(C)C)=O)[CH2:12][CH2:13][O:14][C:15]2[CH:23]=[C:22]3[C:18]([C:19]([Cl:31])=[N:20][N:21]3C(OC(C)(C)C)=O)=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(Cl)Cl.NC1C=C([C@@H](O[Si](CC)(CC)CC)CN(C(OC(C)(C)C)=O)CCOC2C=C3C(C(Cl)=NN3C(OC(C)(C)C)=O)=CC=2)C=CC=1F.[C:96]1([S:102](Cl)(=[O:104])=[O:103])[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=1.C(Cl)Cl.C(O)C(N)(CO)CO>C(Cl)Cl.N1C=CC=CC=1>[Cl:31][C:19]1[C:18]2[C:22](=[CH:23][C:15]([O:14][CH2:13][CH2:12][NH:11][CH2:10][C@@H:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH:1][S:102]([C:96]4[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=4)(=[O:104])=[O:103])[CH:3]=3)[OH:39])=[CH:16][CH:17]=2)[NH:21][N:20]=1.[ClH:31]

Participants

8

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 59370758HCID 59370758, compoundHCID 86642587HCID 86642587, compoundHCID 86642588HCID 86642588, compound

Product 2

HCID 313Hydrochloric AcidHCID 178527541HCID 178527541, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

(R)-Tert-butyl 6-(2-((2-(3-amino-4-fluorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-chloroindazole-1-carboxylate-CH2Cl2 solution [0.5 mL; solution obtained by dissolving (R)-tert-butyl 6-(2-((2-(3-amino-4-fluorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-chloroindazole-1-carboxylate (480 mg) which can be prepared according to the method described in Reference example 70, etc. in dehydrated CH2Cl2 (3.52 mL)] was added with dehydrated pyridine (42 μL), benzenesulfonyl chloride-CH2Cl2 solution [0.5 mL; solution obtained by dissolving benzenesulfonyl chloride (466.3 mg; manufactured by Wako Pure Chemical Industries, Ltd.) in dehydrated CH2Cl2 (4 mL)] and dehydrated CH2Cl2, and the mixture was shaken (600 min−1) overnight at room temperature. To the reaction solution, PS-Trisamine [300 mg (3.6 mmol/g); manufactured by Argonaut] was added and the mixture was shaken (600 min−1) for 5 hours at room temperature. The reaction solution was filtered and the solvent was evaporated by blowing nitrogen gas to the filtrate. The resulting residue was purified by column chromatography (“COLUMN-I”; methanol). The resulting purified product was dissolved in 1,4-dioxane (0.2 mL), added with 4 mol/L-hydrochloric acid-1,4 dioxane solution (1.5 mL), and then shaken (600 min−1) overnight at room temperature. To the reaction solution, nitrogen gas was blown to evaporate the solvent, and the resulting residue was added with MTBE to obtain suspension. Nitrogen gas was blown to the suspension to evaporate the solvent, and as a result, the title compound was obtained as a hydrochloride (40.7 mg).

Workup

  1. customsolution obtained
  2. customcan be prepared
  3. stirringthe mixture was shaken (600 min−1) for 5 hours at room temperature
  4. filtrationThe reaction solution was filtered
  5. customthe solvent was evaporated
  6. customThe resulting residue was purified by column chromatography (“COLUMN-I”; methanol)
  7. customThe resulting purified product
  8. dissolutionwas dissolved in 1,4-dioxane (0.2 mL)
  9. additionadded with 4 mol/L-hydrochloric acid-1,4 dioxane solution (1.5 mL)
  10. stirringshaken (600 min−1) overnight at room temperature
  11. customto evaporate the solvent
  12. additionthe resulting residue was added with MTBE
  13. customto obtain suspension
  14. customto evaporate the solvent

Sources & evidence

ORD record
ord-df30eaa47bad4f6390a9a2a18281a23a
Source dataset
uspto-grants-2012_11
Patent number
US08304443B2

Reaction notes

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