Hydrochloric Acid → HCID 178502473, compound

HRID 1751615Notes

Reaction equation

HRID 1751615 reaction equation
Cl.O1CCOCC1.[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3C(OC(C)(C)C)=O)=[N:18][C:14]=1[CH:13]=[CH:12]2.[CH3:36][O:37][C:38]([NH:40][C@@H:41]([CH:45]([CH3:47])[CH3:46])[C:42](O)=[O:43])=[O:39].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CO>[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3[C:42](=[O:43])[C@@H:41]([NH:40][C:38](=[O:39])[O:37][CH3:36])[CH:45]([CH3:47])[CH3:46])=[N:18][C:14]=1[CH:13]=[CH:12]2

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 178452510HCID 178452510, compound

Product 1

HCID 178502473HCID 178502473, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

Hydrogen chloride in dioxane solution (4N, 6.78 mL, 27.18 mmol) was added to (1S,3S,4R)-tert-butyl 3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (0.80 g, 1.81 mmol) in methylene chloride:methanol (18.1 mL: 3.6 mL). The suspension was allowed to stir at room temperature for one hour. Upon completion by LCMS, the reaction was concentrated to dryness and the crude product (assumed 1.81 mmol) was suspended in methylene chloride (18 mL). (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.38 g, 2.17 mmol) and DIPEA (1.58 mL, 9.04 mmol) were added to the slurry. HATU (1.03 g, 2.71 mmol) was added and the reaction was stirred at room temperature for 3 hours. Upon completion, the crude reaction was diluted in methylene chloride and washed with 1N HCl, and aqueous sodium bicarbonate. The organic layer was concentrated and purified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes) to give methyl (S)-1-((1S,3S,4R)-3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.949, >99%).

Workup

  1. concentrationUpon completion by LCMS, the reaction was concentrated to dryness
  2. stirringthe reaction was stirred at room temperature for 3 hours
  3. customUpon completion, the crude reaction
  4. washwashed with 1N HCl, and aqueous sodium bicarbonate
  5. concentrationThe organic layer was concentrated
  6. custompurified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes)

Sources & evidence

ORD record
ord-75cfc73e60a549e684ebcc8437553a89
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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