Hydrochloric Acid → HCID 67522673, compound

HRID 1751588Notes

Reaction equation

HRID 1751588 reaction equation
[Br:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:17]4[NH:21][C:20]([C@@H:22]5[CH2:26][CH2:25][CH2:24][N:23]5[C:27]([O:29]C(C)(C)C)=O)=[N:19][CH:18]=4)=[CH:10][C:11]=3[C:12]2([F:16])[F:15])=[CH:4][CH:3]=1.Cl.O1CCOCC1.[CH3:41][O:42][C:43]([NH:45][C@@H:46]([CH:50]([CH3:52])[CH3:51])C(O)=O)=[O:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.CO>[Br:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:17]4[NH:21][C:20]([C@@H:22]5[CH2:26][CH2:25][CH2:24][N:23]5[C:27](=[O:29])[C@@H:46]([NH:45][C:43](=[O:44])[O:42][CH3:41])[CH:50]([CH3:52])[CH3:51])=[N:19][CH:18]=4)=[CH:10][C:11]=3[C:12]2([F:15])[F:16])=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 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 59610218HCID 59610218, compound

Product 1

HCID 67522673HCID 67522673, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-tert-butyl 2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.09 g, 2.1 mmol), methanol (10 mL), and 4M HCl in dioxane (10 mL, 40 mmol) was stirred at room temperature. The reaction was thoroughly concentrated after one hour. The resulting residue was dissolved in dimethylformamide (10.6 mL). To this solution was added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (390 mg, 2.2 mmol) and HATU (847 mg, 2.2 mmol). Diisopropylethylamine (1.3 mL, 7.5 mmol) was added and the reaction was stirred at room temperature. After thirty minutes, the reaction was diluted with ethyl acetate. The organic phase was washed with water and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield methyl (S)-1-((S)-2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (712 mg, 59%).

Workup

  1. concentrationThe reaction was thoroughly concentrated after one hour
  2. dissolutionThe resulting residue was dissolved in dimethylformamide (10.6 mL)
  3. waitAfter thirty minutes
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-bf2bcadf11654b84abb1f262e6b23a4c
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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