Trifluoroacetic acid → (S)-N-((R)-1,2,3,4-Tetrahydronaphthalen-1-yl)-7-(((3S,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HRID 339243Notes

Reaction equation

HRID 339243 reaction equation
C(OC([N:8]1[C@H:12]([C:13](=[O:25])[NH:14][C@H:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][CH2:17][CH2:16]2)[CH2:11][C@H:10]([NH:26][C:27]2[CH:36]=[C:35]3[C:30]([CH2:31][C@@H:32]([C:44](=[O:56])[NH:45][C@H:46]4[C:55]5[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=5)[CH2:49][CH2:48][CH2:47]4)[N:33](C(OC(C)(C)C)=O)[CH2:34]3)=[CH:29][CH:28]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C@H:46]1([NH:45][C:44]([C@@H:32]2[CH2:31][C:30]3[C:35](=[CH:36][C:27]([NH:26][C@H:10]4[CH2:11][C@@H:12]([C:13](=[O:25])[NH:14][C@H:15]5[C:24]6[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=6)[CH2:18][CH2:17][CH2:16]5)[NH:8][CH2:9]4)=[CH:28][CH:29]=3)[CH2:34][NH:33]2)=[O:56])[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH2:49][CH2:48][CH2:47]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 86705877(S)-tert-Butyl 7-(((3S,5S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 86705878(S)-N-((R)-1,2,3,4-Tetrahydronaphthalen-1-yl)-7-(((3S,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-1,2,3,4-tetrahydroisoquinoline-3-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 7-(((3S,5S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (150 mg, 0.20 mmol) in CH2Cl2 (2.2 mL) was added TFA (303 μL, 3.93 mmol). The resulting solution was stirred at room temperature for 1 h. Additional TFA (303 μL, 3.93 mmol) was added. The reaction mixture was stirred for 2 h, then quenched carefully with sat. aq. NaHCO3 solution and poured into a separatory funnel containing EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (111 mg, 100%) as a tan solid. MS (ESI+) m/z 564.4 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. customquenched carefully with sat. aq. NaHCO3 solution
  3. additionpoured into a separatory funnel
  4. additioncontaining EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (3×)
  7. washThe combined organics were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96b89f4cbe8a47bd94dcf23a158271df
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

Loading…