Diisopropylethylamine → HCID 58384832, compound

HRID 1945359Notes

Reaction equation

HRID 1945359 reaction equation
Cl.O1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[C:33]([C:36]1[CH:37]=[CH:38][C:39]([CH3:50])=[C:40]([NH:42][C:43]([C@@H:45]2[CH2:49][CH2:48][CH2:47][NH:46]2)=[O:44])[CH:41]=1)(=[O:35])[CH3:34].[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:33]([C:36]1[CH:37]=[CH:38][C:39]([CH3:50])=[C:40]([NH:42][C:43]([C@@H:45]2[CH2:49][CH2:48][CH2:47][N:46]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:44])[CH:41]=1)(=[O:35])[CH3:34]

Participants

8

Reactant 5

HCID 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 66728221HCID 66728221, 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. stirringthe reaction mixture was stirred 18 h
  4. customThe solvent was removed in vacuo
  5. washeluted by gradient 50%-100% B (500 mL)

Sources & evidence

ORD record
ord-2df52be9fb194f50ad34877344cf9f83
Source dataset
uspto-grants-2013_03
Patent number
US08394968B2

Reaction notes

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