Hydrochloric Acid → 2-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride

HRID 387635Notes

Reaction equation

HRID 387635 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18]([NH:20][C@@H:21]([CH2:39][C:40]3[CH:45]=[C:44]([F:46])[CH:43]=[C:42]([F:47])[CH:41]=3)[C@H:22]([OH:38])[CH2:23][NH:24][C:25]3([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=4)[CH2:27][CH2:26]3)=[O:19])=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:48])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:49]>C(OCC)C>[ClH:49].[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18]([NH:20][C@@H:21]([CH2:39][C:40]3[CH:41]=[C:42]([F:47])[CH:43]=[C:44]([F:46])[CH:45]=3)[C@H:22]([OH:38])[CH2:23][NH:24][C:25]3([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:35])([F:37])[F:36])[CH:29]=4)[CH2:27][CH2:26]3)=[O:19])=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]1=[O:48])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 25206293HCID 25206293, compound

Product 1

HCID 252062922-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

At a temperature close to 20° C., 100 mg of 2-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are dissolved in 2 cm3 of ethyl ether. Since the product crystallizes, the ethyl ether is removed under reduced pressure (5 kPa). The residue is dissolved at high temperature in ethyl acetate then the solution obtained is cooled to a temperature close to 0° C. and 0.7 cm3 of a 2M solution of hydrochloric acid in ethyl ether is added. Stirring is continued for 15 min. The solution is then concentrated under reduced pressure (5 kPa). 3 cm3 of ethyl ether are added. The reaction mixture precipitates. The stirring is stopped in order to remove the supernatant, then ethyl ether is again added. This operation is carried out twice. The last suspension is then concentrated under reduced pressure (5 kPa). 94 mg of 2-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride (1:1) are obtained in the form of a pale yellow solid.

Workup

  1. customAt a temperature close to 20° C.
  2. customSince the product crystallizes
  3. customthe ethyl ether is removed under reduced pressure (5 kPa)
  4. dissolutionThe residue is dissolved at high temperature in ethyl acetate
  5. customthe solution obtained
  6. temperatureis cooled to a temperature
  7. customclose to 0° C.
  8. concentrationThe solution is then concentrated under reduced pressure (5 kPa)
  9. addition3 cm3 of ethyl ether are added
  10. customThe reaction mixture precipitates
  11. customto remove the supernatant
  12. additionethyl ether is again added
  13. concentrationThe last suspension is then concentrated under reduced pressure (5 kPa)

Sources & evidence

ORD record
ord-75997eb72f4a4d5ca319ca314b4a0857
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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