1-Hydroxybenzotriazole → N-[(1R)-6-[(4-Fluoro-piperidin-1-yl)-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 1694320Notes

Reaction equation

HRID 1694320 reaction equation
CCN(C(C)C)C(C)C.[S:10]([N:20]1[CH2:25][CH2:24][N:23]2[CH:26]=[CH:27][CH:28]=[C:22]2[CH:21]1[CH2:29][C:30]([OH:32])=O)([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[F:55][CH:56]1[CH2:61][CH2:60][N:59]([CH2:62][C:63]2[CH:64]=[C:65]3[C:70](=[CH:71][CH:72]=2)[CH:69]([NH2:73])[CH2:68][CH2:67][CH2:66]3)[CH2:58][CH2:57]1>C(Cl)Cl>[F:55][CH:56]1[CH2:61][CH2:60][N:59]([CH2:62][C:63]2[CH:64]=[C:65]3[C:70](=[CH:71][CH:72]=2)[C@H:69]([NH:73][C:30](=[O:32])[CH2:29][CH:21]2[N:20]([S:10]([C:13]4[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=4)(=[O:11])=[O:12])[CH2:25][CH2:24][N:23]4[CH:26]=[CH:27][CH:28]=[C:22]24)[CH2:68][CH2:67][CH2:66]3)[CH2:58][CH2:57]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59486400HCID 59486400, compoundHCID 689277936-((4-Fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine

Product 1

HCID 46908499N-[(1R)-6-[(4-Fluoro-piperidin-1-yl)-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 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

DIPEA (630 μl, 3.592 mmol, 4.0 eq.) was added to a stirred 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 DCM (15 ml), followed by EDCl (260 mg, 1.347 mmol, 1.5 eq.) and HOBT (183 mg, 1.347 mmol, 1.5 eq.) which were added at 0° C. The reaction mixture was allowed to stir for 30 min. A solution of R)-6-((4-fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A52) (0.898 mmol, 1.0 eq.) in DCM (5 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The reaction mixture was diluted with DCM (50 ml) and washed with sat. NH4Cl solution (50 ml), sat. NaHCO3 solution (50 ml), water (50 ml) and brine (50 ml), and dried over Na2SO4. The solvent was evaporated under reduced pressure to give crude product which was purified by column chromatography (silica gel; 2% MeOH/DCM) to yield the desired compound as an off white solid. Yield: 38% (197 mg, 0.34 mmol); MS, Rt=3.2 min; m/z=579.1 [M H]+

Workup

  1. additionwere added at 0° C
  2. stirringwas stirred at RT for 16 h
  3. washwashed with sat. NH4Cl solution (50 ml), sat. NaHCO3 solution (50 ml), water (50 ml) and brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. customThe solvent was evaporated under reduced pressure
  6. customto give crude product which
  7. customwas purified by column chromatography (silica gel; 2% MeOH/DCM)

Sources & evidence

ORD record
ord-8b23fa3fde6d4125868e1e22503867fc
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

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