Diisopropylethylamine → 2-(2-Tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)-N-((R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

HRID 1694321Notes

Reaction equation

HRID 1694321 reaction equation
[S:1]([N:11]1[CH2:16][CH2:15][N:14]2[CH:17]=[CH:18][CH:19]=[C:13]2[CH:12]1[CH2:20][C:21]([OH:23])=O)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:57][C:58]([F:74])([F:73])[CH2:59][NH:60][CH2:61][C:62]1[CH:63]=[C:64]2[C:69](=[CH:70][CH:71]=1)[C@H:68]([NH2:72])[CH2:67][CH2:66][CH2:65]2>C1COCC1>[S:1]([N:11]1[CH2:16][CH2:15][N:14]2[CH:17]=[CH:18][CH:19]=[C:13]2[CH:12]1[CH2:20][C:21]([NH:72][C@H:68]1[C:69]2[C:64](=[CH:63][C:62]([CH2:61][NH:60][CH2:59][C:58]([F:57])([F:73])[F:74])=[CH:71][CH:70]=2)[CH2:65][CH2:66][CH2:67]1)=[O:23])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59486384(R)-6-((2,2,2-Trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amineHCID 59486400HCID 59486400, compound

Product 1

HCID 469085002-(2-Tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)-N-((R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamideYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (214 mg, 0.64 mmol, 1.0 eq.) in THF (5 ml) were added DIPEA (340 μl, 1.92 mmol, 3.0 eq.) and HATU (292 mg, 0.77 mmol, 1.2 eq.) at 0° C. and the mixture was stirred for 15 min at the same temperature. A solution of (R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A53) (0.64 mmol, 1.0 eq.) in THF (5 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The reaction mixture was concentrated and the residue was diluted with DCM (50 ml) and washed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 0.7% MeOH/DCM) to yield the desired product as an off-white solid. Yield: 22% (80 mg, 0.14 mmol); MS, Rt=3.2 min; m/z=575.0 [MH]+

Workup

  1. stirringwas stirred at RT for 16 h
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with DCM (50 ml)
  4. washwashed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product which
  8. customwas purified by column chromatography (silica gel; 0.7% MeOH/DCM)

Sources & evidence

ORD record
ord-0f932903c66a497c853dae197a2bd397
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

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