Diisopropylethylamine → N-[2-[4-(4,5-Dihydro-1H-imidazol-2-yl)-phenyl]-ethyl]-2-[2-[(6-methoxy-naphthalen-2-yl)sulfonyl]-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-1-yl]-acetamide

HRID 1694317Notes

Reaction equation

HRID 1694317 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[CH:33]=[C:32]([S:37]([N:40]1[CH2:45][CH2:44][N:43]3[CH:46]=[CH:47][CH:48]=[C:42]3[CH:41]1[CH2:49][C:50]([OH:52])=O)(=[O:39])=[O:38])[CH:31]=[CH:30]2.[NH:53]1[CH2:57][CH2:56][N:55]=[C:54]1[C:58]1[CH:63]=[CH:62][C:61]([CH2:64][CH2:65][NH2:66])=[CH:60][CH:59]=1.CCN(C(C)C)C(C)C>C1COCC1>[NH:55]1[CH2:56][CH2:57][N:53]=[C:54]1[C:58]1[CH:59]=[CH:60][C:61]([CH2:64][CH2:65][NH:66][C:50](=[O:52])[CH2:49][CH:41]2[N:40]([S:37]([C:32]3[CH:31]=[CH:30][C:29]4[C:34](=[CH:35][CH:36]=[C:27]([O:26][CH3:25])[CH:28]=4)[CH:33]=3)(=[O:38])=[O:39])[CH2:45][CH2:44][N:43]3[CH:46]=[CH:47][CH:48]=[C:42]23)=[CH:62][CH:63]=1

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 223907052-[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]ethan-1-amineHCID 594864212-(2-(6-Methoxynaphthalen-2-ylsulfonyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid

Product 1

HCID 46908410N-[2-[4-(4,5-Dihydro-1H-imidazol-2-yl)-phenyl]-ethyl]-2-[2-[(6-methoxy-naphthalen-2-yl)sulfonyl]-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-1-yl]-acetamideYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HATU (563 mg, 1.48 mmol, 2.0 eq.) was added to a mixture of 2-(2-(6-methoxynaphthalen-2-ylsulfonyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S-2) (297 mg, 0.74 mmol, 1.0 eq.), 2-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl)ethanamine (A49) (140 mg, 0.74 mmol, 1.0 eq.), and DIPEA (0.39 ml, 2.22 mmol, 3.0 eq.) in THF (10 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 14 h. The solvent was evaporated under reduced pressure, the residue dissolved in DCM (30 ml) and washed with saturated ammonium chloride solution (15 ml), saturated sodium bicarbonate solution (15 ml), water (15 ml) and brine (15 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to yield the crude product which was purified by column chromatography (neutral alumina; 1% MeOH/DCM) to afford the desired product as an off-white solid. Yield: 35% (140 mg, 0.245 mmol); MS, Rt=3.3 min; m/z=572.5 [MH]+

Workup

  1. customthe resulting reaction mixture
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue dissolved in DCM (30 ml)
  4. washwashed with saturated ammonium chloride solution (15 ml), saturated sodium bicarbonate solution (15 ml), water (15 ml) and brine (15 ml)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto yield the crude product which
  8. customwas purified by column chromatography (neutral alumina; 1% MeOH/DCM)

Sources & evidence

ORD record
ord-e8eccae2e9cd4287885d2bcd44781204
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

Loading…