Hydrochloric Acid → HCID 131731599, compound

HRID 404607Notes

Reaction equation

HRID 404607 reaction equation
[OH-:1].[K+].FC(F)(F)C([N:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][C:11]([S:17]([NH:20][CH2:21][CH2:22][C@@H:23]3[CH2:27][CH2:26][CH2:25][N:24]3[CH3:28])(=[O:19])=[O:18])=[CH:12][CH:13]=2)[CH2:8]1)=[O:6].[ClH:31]>>[OH2:6].[ClH:31].[ClH:31].[CH3:28][N:24]1[CH2:25][CH2:26][CH2:27][C@H:23]1[CH2:22][CH2:21][NH:20][S:17]([C:11]1[CH:10]=[C:9]2[C:14]([CH2:15][CH2:16][NH:7][CH2:8]2)=[CH:13][CH:12]=1)(=[O:19])=[O:18].[OH2:1].[OH2:6].[CH3:28][N:24]1[CH2:25][CH2:26][CH2:27][C@H:23]1[CH2:22][CH2:21][NH:20][S:17]([C:11]1[CH:10]=[C:9]2[C:14]([CH2:15][CH2:16][NH:7][CH2:8]2)=[CH:13][CH:12]=1)(=[O:19])=[O:18].[ClH:31].[ClH:31]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 53378119HCID 53378119, compound

Product 1

HCID 131731599HCID 131731599, compoundYield 87.5%

Procedure

A 45.7% solution of potassium hydroxide (105 g, 0.855 mol) was added to a 30.66% (w/w) ethanolic solution of 2-(2,2,2-trifluoroacetyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide (1023.6, 0.748 mol) at a rate that limited the temperature to no more than 45° C. After cooling to room temperature, the reaction was monitored by HPLC. Upon completion of the deprotection, the reaction was acidified by the dropwise addition of concentrated hydrochloric acid (194 mL, 2.35 mol). The precipitated KCl was removed by filtration at between 39-51° C. The reactor was rinsed with ethanol (300 mL) which in turn was used to rinse the collected KCl. The ethanol filtrates were combined and returned to the reactor. The reactor was heated to approximately 55° C. and 2-methyltetrahydrofuran (375 mL) was added. Seed crystals of N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide dihydrochloride sesquihydrate (1 g) were added. After cooling to approximately −5° C., the product was collected by filtration. The product was rinsed with a solution prepared from 2-methyltetrahydrofuran (200 mL), ethanol (200 mL) and water (5 mL). Following drying in a vacuum oven at 40° C., 277 g (87%) of N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide dihydrochloride sesquihydrate was isolated as a colorless solid.

Workup

  1. customThe precipitated KCl was removed by filtration at between 39-51° C
  2. washThe reactor was rinsed with ethanol (300 mL) which in turn
  3. washto rinse the collected KCl
  4. temperatureThe reactor was heated to approximately 55° C.
  5. addition2-methyltetrahydrofuran (375 mL) was added
  6. additionSeed crystals of N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide dihydrochloride sesquihydrate (1 g) were added
  7. temperatureAfter cooling to approximately −5° C.
  8. filtrationthe product was collected by filtration
  9. washThe product was rinsed with a solution
  10. customprepared from 2-methyltetrahydrofuran (200 mL), ethanol (200 mL) and water (5 mL)
  11. customFollowing drying in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-dfcf5fc0fd3b44c983f30d8c4cdcc1b6
Source dataset
uspto-grants-2014_06
Patent number
US08748615B2

Reaction notes

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