Hydrochloric Acid → HCID 89815245, compound

HRID 2172283Notes

Reaction equation

HRID 2172283 reaction equation
[CH3:1][C:2]1([CH3:26])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[CH2:11][CH2:12][N:13](C(OC(C)(C)C)=O)[CH2:14]3)[O:3]1.Cl.O1CCOCC1.[S:34]1[C:38]([NH2:39])=[N:37][CH:36]=[N:35]1.C(N(CC)CC)C.[S:47](Cl)(Cl)(=[O:49])=[O:48]>C1COCC1.C(Cl)Cl>[CH3:7][C:6]1([CH3:8])[C:2]([CH3:26])([CH3:1])[O:3][B:4]([C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[CH2:11][CH2:12][N:13]([S:47]([NH:39][C:38]2[S:34][N:35]=[CH:36][N:37]=2)(=[O:49])=[O:48])[CH2:14]3)[O:5]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 24648Sulfuryl chlorideHCID 312751,4-DioxaneHCID 2902745-Amino-1,2,4-thiadiazoleHCID 57505885tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 89815245HCID 89815245, compoundYield 25.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (ASW Medchem, Brunswick, N.J., 2.340 g, 6.51 mmol) in 7 mL THF was treated with HCl 4 N in dioxane (8.14 ml, 32.6 mmol) and was allowed to stir at room temperature overnight. LC/MS showed mostly product, so the reaction mixture was concentrated. The resulting residue was triturated with heptane, and the solid was dried and collected. A separate flask charged with 1,2,4-thiadiazol-5-amine (1.317 g, 13.03 mmol), 26 mL DCM, and triethylamine (4.54 ml, 32.6 mmol) was cooled to −78° C. and was treated with sulfuryl chloride (1.059 ml, 13.03 mmol). After stirring for one hour, the reaction mixture was filtered through a syringe filter and was treated with the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline derived above. After stirring overnight, LC/MS showed product so the reaction mixture was filtered then concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.711 g, 1.684 mmol). [M+H]+=423.3

Workup

  1. concentrationso the reaction mixture was concentrated
  2. customThe resulting residue was triturated with heptane
  3. customthe solid was dried
  4. customcollected
  5. temperaturewas cooled to −78° C.
  6. stirringAfter stirring for one hour
  7. filtrationthe reaction mixture was filtered through a syringe
  8. filtrationfilter
  9. additionwas treated with the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline
  10. stirringAfter stirring overnight
  11. filtrationwas filtered
  12. concentrationthen concentrated
  13. customPurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Sources & evidence

ORD record
ord-ea45ec04d44a40538d6c264a562f62dc
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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