1-Hydroxybenzotriazole → (3aR,6aS)-tert-butyl 5-(5-(2-(trifluoromethyl)benzylcarbamoyl)pyridin-3-yl)hexahydropyrrolo [3,4-c]pyrrole-2(1H)-carboxylate

HRID 240505Notes

Reaction equation

HRID 240505 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]2[CH2:13][N:14]([C:16]3[CH:17]=[N:18][CH:19]=[C:20]([CH:24]=3)[C:21](O)=[O:22])[CH2:15][C@H:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:25][C:26]([F:36])([F:35])[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH2:30].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[F:25][C:26]([F:35])([F:36])[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH:30][C:21]([C:20]1[CH:24]=[C:16]([N:14]2[CH2:15][C@@H:10]3[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:12][C@@H:11]3[CH2:13]2)[CH:17]=[N:18][CH:19]=1)=[O:22]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 764472-(Trifluoromethyl)benzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672653675-((3aR,6aS)-5-(tert-butoxycarbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)nicotinic Acid

Product 1

HCID 67265605(3aR,6aS)-tert-butyl 5-(5-(2-(trifluoromethyl)benzylcarbamoyl)pyridin-3-yl)hexahydropyrrolo [3,4-c]pyrrole-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
33 °C

Procedure

A suspension of the product from Example 33B (52.5 mg, 0.16 mmol), 2-trifluoromethylbenzylamine (33.3 mg, 0.19 mmol), 1-hydroxybenzotriazole (30.1 mg, 0.20 mmol), 4-dimethylaminopyridine (4 mg, 0.03 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34.3 mg, 0.24 mmol) in pyridine (7.0 mL) were stirred at 33° C. for 18 h. The reaction mixture was filtered through a glass microfiber frit and rinsed with methanol. The filtrate was concentrated and the residue was purified by silica gel chromatography (EtOAc, Rf=0.2) to afford the title compound. MS (APCI) m/z 491 (M+H)+.

Workup

  1. filtrationThe reaction mixture was filtered through a glass microfiber frit
  2. washrinsed with methanol
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by silica gel chromatography (EtOAc, Rf=0.2)

Sources & evidence

ORD record
ord-1a36cd94b3584c37af8644d1f0165c7c
Source dataset
uspto-grants-2014_02
Patent number
US08648084B2

Reaction notes

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