Hydrochloric Acid → HCID 89910506, compound

HRID 1524255Notes

Reaction equation

HRID 1524255 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][C@H:15]([CH3:18])[N:14]3[C:19](OC(C)(C)C)=[O:20])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.[CH3:27][O:28][C:29]([NH:31][C@@H:32]([CH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)C(O)=O)=[O:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][C@H:15]([CH3:18])[N:14]3[C:19](=[O:20])[C@@H:32]([NH:31][C:29](=[O:30])[O:28][CH3:27])[CH:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[N:10][CH:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58209599HCID 58209599, compoundHCID 59264488(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid

Product 1

HCID 89910506HCID 89910506, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (2S,5S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (0.50 g, 1.23 mmol) in a mixture of CH2CL2 (10 mL) and methanol (1.0 mL) was added HCl (4M in dioxane, 6.00 mL, 24 mmol). The solution was stirred at 40° C. for 1 h, cooled to room temperature and concentrated to dryness. The crude solid was suspended in CH2CL2 (10 mL), followed by the addition of (S)-2-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (0.298 g, 1.37 mmol), HATU (0.562 g, 1.48 mmol) and DIPEA (0.60 mL, 3.44 mmol). The resulting solution was stirred at room temperature for 18 h. The solution was diluted with CH2CL2 and washed with a mixture of sodium bicarbonate (aqueous, sat) and brine. The aqueous layer was back-extracted with CH2CL2. The combined organic layers were dried over Na2SO4 and concentrated to provide a crude oil. Purification by column chromatography (SiO2, 10-100% EtOAc (10% MeOH)/Hexanes) provided methyl (S)-2-((2S,5S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-5-methylpyrrolidin-1-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate (0.614 g, 99%). MS (ESI) m/z 505.844 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated to dryness
  3. stirringThe resulting solution was stirred at room temperature for 18 h
  4. additionThe solution was diluted with CH2CL2
  5. washwashed with a mixture of sodium bicarbonate (aqueous, sat) and brine
  6. extractionThe aqueous layer was back-extracted with CH2CL2
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. customto provide a crude oil
  10. customPurification by column chromatography (SiO2, 10-100% EtOAc (10% MeOH)/Hexanes)

Sources & evidence

ORD record
ord-6ad7e767fc734b90b9d4b120fe728cd2
Source dataset
uspto-grants-2015_07
Patent number
US09079887B2

Reaction notes

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