Tris(hydroxymethyl)aminomethane → Hydrochloric Acid

HRID 1678724Notes

Reaction equation

HRID 1678724 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]([CH3:31])=[N:20][N:21]3C(OC(C)(C)C)=O)=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(Cl)Cl.NC1C=C([C@@H](O[Si](CC)(CC)CC)CN(C(OC(C)(C)C)=O)CCOC2C=C3C(C(C)=NN3C(OC(C)(C)C)=O)=CC=2)C=CC=1Cl.[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:8][C:7]1[CH:6]=[CH:5][C:4]([C@@H:9]([OH:39])[CH2:10][NH:11][CH2:12][CH2:13][O:14][C:15]2[CH:23]=[C:22]3[C:18]([C:19]([CH3:31])=[N:20][NH:21]3)=[CH:17][CH:16]=2)=[CH:3][C:2]=1[NH:1][S:102]([C:96]1[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=1)(=[O:104])=[O:103].[ClH:8]

Participants

8

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 59373765HCID 59373765, compoundHCID 86642588HCID 86642588, compoundHCID 86642729HCID 86642729, compound

Product 2

HCID 313Hydrochloric AcidHCID 178434359HCID 178434359, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A (R)-tert-butyl 6-(2-((2-(3-amino-4-chlorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-methylindazole-1-carboxylate-CH2Cl2 solution [0.5 mL; solution prepared by dissolving (R)-tert-butyl 6-(2-((2-(3-amino-4-chlorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-methylindazole-1-carboxylate (1.324 g) that can be produced by the method described in Reference Example 101 or the like in dehydrated CH2Cl2 (10 mL)], dehydrated pyridine (42 μL), a benzenesulfonyl chloride-CH2Cl2 solution [0.5 mL; solution prepared by dissolving benzenesulfonyl chloride (466.3 mg; manufactured by Wako Pure Chemical Industries, Ltd.) in dehydrated CH2Cl2 (4 mL)], and dehydrated CH2Cl2 were added, and the mixture was shaken (600 min−1) overnight at room temperature. PS-Trisamine [300 mg (3.6 mmol/g); manufactured by Argonaut Technologies, Inc.] was added to the reaction solution, and the mixture was shaken (600 min−1) for 5 hours at room temperature. The reaction solution was filtered, and nitrogen gas was blown into the filtrate to evaporate the solvent. The resulting residue was purified by column chromatography (“COLUMN-I”; methanol). The obtained purification product was dissolved in 1,4-dioxane (0.2 mL), and a 4 mol/L hydrochloric acid-1,4-dioxane solution (1.5 mL) was added thereto. The mixture was shaken (600 min−1) overnight at room temperature. Nitrogen gas was blown into the reaction solution to evaporate the solvent, and MTBE was added to the obtained residue to obtain a suspension. Nitrogen gas was blown into the suspension to evaporate the solvent, and thus the title compound was obtained in the form of hydrochloride (46.4 mg).

Workup

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

Sources & evidence

ORD record
ord-02cca5dafdc54ad7868cfcb2b043034f
Source dataset
uspto-grants-2011_08
Patent number
US08008506B2

Reaction notes

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