Diisopropylethylamine → (1-(Hydroxymethyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

HRID 60995Notes

Reaction equation

HRID 60995 reaction equation
[CH:1]1([CH2:9][OH:10])[CH:5]2[CH2:6][CH2:7][CH2:8][CH:4]2[CH2:3][NH:2]1.CCN(C(C)C)C(C)C.[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([N:30]2[N:34]=[CH:33][CH:32]=[N:31]2)=[C:25]([CH:29]=1)[C:26](O)=[O:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:10][CH2:9][CH:1]1[CH:5]2[CH2:6][CH2:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:26]([C:25]1[CH:29]=[C:21]([CH3:20])[CH:22]=[CH:23][C:24]=1[N:30]1[N:34]=[CH:33][CH:32]=[N:31]1)=[O:27]

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 532601655-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acidHCID 72429858Octahydro-cyclopenta[c]pyrrole-1-methanol

Product 1

HCID 117727946(1-(Hydroxymethyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the carbamate above in DCM was added TFA (1:1 v/v). The reaction was stirred at rt for 30 min before being concentrated in vacuo. The crude residue was taken up in EtOAc, and washed with satd. aq. NaHCO3, brine, dried (MgSO4), and concentrated to afford (octahydrocyclopenta[c]pyrrol-1-yl)methanol as a pale yellow oil. To a solution of (octahydrocyclopenta[c]pyrrol-1-yl)methanol (1 equiv.) from the previous step in DMF was added DIPEA (2 equiv.) followed by 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid (1.5 equiv.) and HATU (2 equiv.). The reaction was allowed to stir at rt for 15 h, and was then concentrated in vacuo to remove the DMF. The crude residue was taken up in EtOAc and washed with 1 M HCl, sat aq. NaHCO3, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hexanes) to give the title compound as a clear oil. MS (ESI) 326 (M+H).

Workup

  1. concentrationwas then concentrated in vacuo
  2. customto remove the DMF
  3. washwashed with 1 M HCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified by chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-600d7ccd2b8c43adbdc2979827fcab31
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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