1-Hydroxybenzotriazole → HCID 66861615, compound

HRID 2060769Notes

Reaction equation

HRID 2060769 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:17][CH2:16][O:15][CH2:14][CH:13]2[CH2:12][S:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([C:33](O)=[O:34])=[N:31][CH:32]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C=O)C.O.[OH-].[Na+]>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]([NH:1][C:2]2[CH:3]=[C:4]([C@:8]34[CH2:17][CH2:16][O:15][CH2:14][CH:13]3[CH2:12][S:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[N:9]4)[CH:5]=[CH:6][CH:7]=2)=[O:34])=[N:31][CH:32]=1

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628725-Chloro-2-picolinic acidHCID 57504900HCID 57504900, compound

Product 1

HCID 66861615HCID 66861615, compoundYield 85%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a mixture of tert-butyl (8aS)-8a-(3-aminophenyl)-4,4a,5,7,8,8a-hexahydropyrano[4,3-d][1,3]thiazin-2-ylcarbamate (0.15 g, 0.413 mmol), 5-chloropyridine-2-carboxylic acid (0.078 g, 0.495 mmol) and 1-hydroxybenzotriazole (0.073 g, 0.536 mmol) in CH2Cl2 (2.75 mL) and DMF (0.3 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.103 g, 0.536 mmol). The reaction is stirred overnight at room temperature. The reaction mixture is diluted with water, 5 N NaOH (0.5 mL) and extracted three times with CH2Cl2. The combined organic layer is dried over Na2SO4 and the crude product is purified by silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes to give the title compound (0.176 g, 85%). ES/MS m/e: (35Cl/37Cl) 503, 505 (M+1).

Workup

  1. extractionextracted three times with CH2Cl2
  2. dry with materialThe combined organic layer is dried over Na2SO4
  3. customthe crude product is purified by silica gel chromatography
  4. washeluting with a linear gradient of 5% to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-484dc9ca7c274a2daf9be3d53818ba1f
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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