Hydrochloric Acid → HCID 86702344, compound

HRID 1524256Notes

Reaction equation

HRID 1524256 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7](C(OC(C)(C)C)=O)[C@H:6]([C:16]2[NH:17][C:18]([C:21]3[CH:26]=[CH:25][C:24]([B:27]4[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]4)=[CH:23][CH:22]=3)=[CH:19][N:20]=2)[CH2:5]1.Cl.[CH3:37][O:38][C:39]([NH:41][C@@H:42]([CH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1)[C:43](O)=[O:44])=[O:40].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>C(Cl)Cl.CO>[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7]([C:43](=[O:44])[C@@H:42]([NH:41][C:39](=[O:40])[O:38][CH3:37])[CH:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)[C@H:6]([C:16]2[NH:17][C:18]([C:21]3[CH:26]=[CH:25][C:24]([B:27]4[O:28][C:29]([CH3:34])([CH3:35])[C:30]([CH3:32])([CH3:33])[O:31]4)=[CH:23][CH:22]=3)=[CH:19][N:20]=2)[CH2:5]1

Participants

8

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 59264488(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 67682602HCID 67682602, compound

Product 1

HCID 86702344HCID 86702344, compoundYield 80.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (2S,4S)-tert-butyl 4-(methoxymethyl)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (0.50 g, 1.03 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 (0.260 g, 1.20 mmol), HATU (0.475 g, 1.25 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,4S)-4-(methoxymethyl)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate (0.483 g, 80%). MS (ESI) m/z 583.333 [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-a3483776176a4240a068da9ec53fcb95
Source dataset
uspto-grants-2015_07
Patent number
US09079887B2

Reaction notes

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