Trifluoroacetic acid → 4'-Methyl-N-((6-methylpyridin-3-yl)methyl)-5-((3aR,6aS)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)biphenyl-3-carboxamide

HRID 1845228Notes

Reaction equation

HRID 1845228 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14](=[O:24])[NH:15][CH2:16][C:17]3[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=3)[CH:11]=[C:10]([C:25](O)=[O:26])[CH:9]=2)=[CH:4][CH:3]=1.[CH2:28]1[C@@H:32]2[CH2:33][NH:34][CH2:35][C@@H:31]2[CH2:30][N:29]1C(OC(C)(C)C)=O.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O>CN(C)C=O.C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([C:25]([N:29]3[CH2:30][C@@H:31]4[C@@H:32]([CH2:33][NH:34][CH2:35]4)[CH2:28]3)=[O:26])[CH:11]=[C:12]([C:14]([NH:15][CH2:16][C:17]3[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=3)=[O:24])[CH:13]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 1514452Cis-2-boc-hexahydropyrrolo[3,4-C]pyrroleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581880514'-Methyl-5-((6-methylpyridin-3-yl)methylcarbamoyl)biphenyl-3-carboxylic acid

Product 1

HCID 581879984'-Methyl-N-((6-methylpyridin-3-yl)methyl)-5-((3aR,6aS)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4′-methyl-5-((6-methylpyridin-3-yl)methylcarbamoyl)-biphenyl-3-carboxylic acid (25 mg, 0.069 mmol) in N,N-dimethylformamide (1 mL) were added (3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (30 mg, 0.14 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (60 mg, 0.16 mmol) and N,N-diisopropylethylamine (100 μL, 0.57 mmol). The reaction mixture was stirred for 16 hours at 25° C. The reaction mixture was purified by preparative HPLC to yield Boc protected product as a white solid, which was dissolved in methylene chloride (3.0 mL) and trifluoroacetic acid (0.20 mL, 2.6 mmol) was added. The reaction mixture was stirred at rt overnight. The volatiles were removed in vacuo and the residue was purified by preparative HPLC (100×21.2 mm C18 column, 20-60% MeCN/water[10 mM Et2NH]) to afford the product as a white foam.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. customto yield Boc protected product as a white solid, which
  3. stirringThe reaction mixture was stirred at rt overnight
  4. customThe volatiles were removed in vacuo
  5. customthe residue was purified by preparative HPLC (100×21.2 mm C18 column, 20-60% MeCN/water[10 mM Et2NH])

Sources & evidence

ORD record
ord-fdd27f248e6a4aae98ac7cada5fa411f
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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