Diisopropylethylamine → methyl (S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-4,4-difluoropyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate

HRID 709360Notes

Reaction equation

HRID 709360 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7](O)=[O:8])=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[NH:48][C:47]([C@@H:49]3[CH2:53][C:52]([F:55])([F:54])[CH2:51][NH:50]3)=[N:46][CH:45]=2)=[CH:40][CH:39]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[NH:48][C:47]([C@@H:49]3[CH2:53][C:52]([F:54])([F:55])[CH2:51][N:50]3[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:10]([CH3:12])[CH3:11])=[N:46][CH:45]=2)=[CH:40][CH:39]=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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 70663897HCID 70663897, compound

Product 1

HCID 86670830methyl (S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-4,4-difluoropyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

In a 20 ml, pear-shaped flask, (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (416 mg, 2.38 mmol) and HATU (695 mg, 1.83 mmol) were combined with DMF (10 ml) to give a colorless solution. (S)-5-(4-bromophenyl)-2-(4,4-difluoropyrrolidin-2-yl)-1H-imidazole (600 mg, 1.83 mmol) in 2 ml of DMF was added and followed by drop wise addition of DIPEA (1.18 g, 1.6 ml, 9.14 mmol). It was stirred at room temperature for 1 hr then poured into ice/water. It was extracted with EtOAc (2×30 ml), washed with brine and water. The organic layer was dried over MgSO4, concentrated and purified on a silica gel column (CH2Cl2, 1%, 2%, 5% MeOH/CH2Cl2) to afford methyl (S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-4,4-difluoropyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate as an orange foaming solid. (650 mg, 73%): ESI-LRMS m/e calcd for C20H25BrF2N4O3 [M+] 485. found 486 [M+H+].

Workup

  1. customto give a colorless solution
  2. extractionIt was extracted with EtOAc (2×30 ml)
  3. washwashed with brine and water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. custompurified on a silica gel column (CH2Cl2, 1%, 2%, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-dd1388f9cb1e481394f55875b9c2552b
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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