Hydrochloric Acid → HCID 58384832, compound

HRID 2407594Notes

Reaction equation

HRID 2407594 reaction equation
Cl.O1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:32]([C:35]1[CH:36]=[CH:37][C:38]([CH3:49])=[C:39]([NH:41][C:42]([C@@H:44]2[CH2:48][CH2:47][CH2:46][NH:45]2)=[O:43])[CH:40]=1)(=[O:34])[CH3:33].Cl.[CH3:51][O:52][C:53]([NH:55][C@H:56]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C:57](O)=[O:58])=[O:54].CCN(C(C)C)C(C)C>CO.CN(C)C=O>[C:32]([C:35]1[CH:36]=[CH:37][C:38]([CH3:49])=[C:39]([NH:41][C:42]([C@@H:44]2[CH2:48][CH2:47][CH2:46][N:45]2[C:57](=[O:58])[C@H:56]([NH:55][C:53](=[O:54])[O:52][CH3:51])[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[O:43])[CH:40]=1)(=[O:34])[CH3:33]

Participants

9

Reactant 6

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 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 204431481,4-Dioxane hydrochlorideHCID 66728213HCID 66728213, compound

Product 1

HCID 58384832HCID 58384832, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Example J.38 (3 g, 83 mmol) was dissolved in methanol (30 mL) and 4N HCl/dioxane (50 mL) was added and the reaction was stirred 18 hr. The solvents were removed in vacuo, and (S)—N-(5-acetyl-2-methylphenyl)pyrrolidine-2-carboxamide HCl salt was exposed to vacuum. LC (Cond-J1): 0.9 min. HATU (1.4 g, 3.5 mmol) was added in one portion to a stirred solution of (S)—N-(5-acetyl-2-methylphenyl)pyrrolidine-2-carboxamide.HCl (1.0 g, 3.5 mmol), (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (740 mg, 3.5 mmol), and Hunig's base (2.9 mL) in dimethylformamide (25 mL) and the reaction mixture was stirred 18 h. The solvent was removed in vacuo and the residue was applied to a 40 M Biotage SiO2 column, and eluted by gradient 50%-100% B (500 mL); A=hexanes; B=ethyl acetate to give J.39, methyl (R)-2-((S)-2-(5-acetyl-2-methylphenylcarbamoyl)pyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamate 1.25 g (87%). 1H NMR (300 MHz, DMSO-d6) δ: 9.42 (s, 1H), 7.95 (s, 1H), 7.75-7.69 (m, 2H), 7.43-7.19 (m, 6H), 5.50/5.40 (d, J=7.7 Hz, 1H), 4.49-4.47 (m, 1H), 3.87-3.81 (m, 1H), 3.58-3.54 (m, 1H), 3.50 (s, 3H), 2.54 (s, 3H), 2.27 (s, 3H), 1.99-1.83 (m, 4H). LC (Cond.-J1): 1.65 min; LRMS: Anal. Calcd. for [M+H]+ C24H28N3O5: 438.20; found 438.20.

Workup

  1. customThe solvents were removed in vacuo, and (S)—N-(5-acetyl-2-methylphenyl)pyrrolidine-2-carboxamide HCl salt
  2. custom0.9 min
  3. customThe solvent was removed in vacuo
  4. washeluted by gradient 50%-100% B (500 mL)

Sources & evidence

ORD record
ord-1f62dad50f0c4537bfa1b9d338782878
Source dataset
uspto-grants-2014_08
Patent number
US08809548B2

Reaction notes

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