Diisopropylethylamine → N-[(1R)-6-[(tert-Butylamino)-methyl]-1,2,3,4-tetrahydro-naphthalen-1-yl]-2-[2-(p-tolylsulfonyl)-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-1-yl]-acetamide

HRID 1694318Notes

Reaction equation

HRID 1694318 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](O)=[O:22])([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.[C:57]([NH:61][CH2:62][C:63]1[CH:64]=[C:65]2[C:70](=[CH:71][CH:72]=1)[C@H:69]([NH2:73])[CH2:68][CH2:67][CH2:66]2)([CH3:60])([CH3:59])[CH3:58]>C1COCC1.C(OCC)(=O)C>[C:57]([NH:61][CH2:62][C:63]1[CH:64]=[C:65]2[C:70](=[CH:71][CH:72]=1)[C@H:69]([NH:73][C:21](=[O:22])[CH2:20][CH:12]1[N:11]([S:1]([C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=3)(=[O:2])=[O:3])[CH2:16][CH2:15][N:14]3[CH:17]=[CH:18][CH:19]=[C:13]13)[CH2:68][CH2:67][CH2:66]2)([CH3:60])([CH3:58])[CH3:59]

Participants

7

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 58645992(R)-6-((tert-butylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amineHCID 59486400HCID 59486400, compound

Product 1

HCID 46908411N-[(1R)-6-[(tert-Butylamino)-methyl]-1,2,3,4-tetrahydro-naphthalen-1-yl]-2-[2-(p-tolylsulfonyl)-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-1-yl]-acetamideYield 19%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (300 mg, 0.898 mmol, 1.0 eq.) in THF (5 ml) were added DIPEA (0.47 ml, 2.694 mmol, 3.0 eq.) and HATU (410 mg, 1.08 mmol, 1.2 eq.) at 0° C. and the mixture was stirred for 15 min at the same temperature. A solution of (R)-6-((tert-butylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A50) (0.898 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 diluted with ethyl acetate (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 get the crude product which was purified by column chromatography (silica gel; 1.5% MeOH/DCM) to yield the desired product as an off-white solid. Yield: 19% (94 mg, 0.171 mmol); MS, Rt=3.2 min; m/z=549.1 [MH]+

Workup

  1. stirringwas stirred at RT for 16 h
  2. washwashed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto get the crude product which
  6. customwas purified by column chromatography (silica gel; 1.5% MeOH/DCM)

Sources & evidence

ORD record
ord-5cf70bbac4d74f66aebe469e63601bb6
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

Loading…