Sodium Hydroxide → HCID 24995282, compound

HRID 911096Notes

Reaction equation

HRID 911096 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:18]=[C:17]([NH:19][C:20]3[CH:25]=[C:24]([O:26][C:27]4[C:28]([CH3:39])=[N:29][CH:30]=[C:31]([C:37]=4[CH3:38])[C:32](OCC)=[O:33])[C:23]([Br:40])=[CH:22][N:21]=3)[S:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[CH3:43][N:44]([CH3:48])[CH2:45][CH2:46][NH2:47].Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.O>CCO.CN(C=O)C.O>[CH3:43][N:44]([CH3:48])[CH2:45][CH2:46][NH:47][C:32]([C:31]1[C:37]([CH3:38])=[C:27]([O:26][C:24]2[C:23]([Br:40])=[CH:22][N:21]=[C:20]([NH:19][C:17]3[S:16][N:15]=[C:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]4)[N:18]=3)[CH:25]=2)[C:28]([CH3:39])=[N:29][CH:30]=1)=[O:33]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 66053N,N-DimethylethylenediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57899006HCID 57899006, compound

Product 1

HCID 24995282HCID 24995282, compoundYield 56.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl 5-(2-(3-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1,2,4-thiadiazol-5-ylamino)-5-bromopyridin-4-yloxy)-4,6-dimethylnicotinate (0.50 g, 0.79 mmol) was dissolved in EtOH (10 mL). NaOH (1N in H2O, 2.0 ml, 2.0 mmol) was added. The reaction stirred at 60° C. for 3 hours. The solution was cooled and concentrated to give the hydrolyzed product as a yellow salt. This residue was re-dissolved in DMF (2 mL). N1,N1-dimethylethane-1,2-diamine (0.31 ml, 2.8 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.45 g, 2.4 mmol) and HOBT-H2O (0.36 g, 2.4 mmol) were added. The reaction stirred at 50° C. for 2 hours. The solution was cooled, diluted with water (15 mL), extracted with EtOAc, dried, and concentrated. Flash chromatography (DCM-15% MeOH/DCM/0.1-1% NH4OH) gave tert-butyl 4-(5-(4-(5-((2-(dimethylamino)ethyl)carbamoyl)-2,4-dimethylpyridin-3-yloxy)-5-bromopyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (0.30 g, 56%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 1.45 (s, 9H), 1.70-1.77 (m, 2H), 1.95-1.99 (m, 2H), 2.25 (s, 3H), 2.29 (s, 6H), 2.39 (s, 3H), 2.56-2.62 (m, 2H), 2.85-2.89 (m 3H), 3.52-2.64 (m, 2H), 4.08-4.15 (m, 2H), 5.95 (s, 1H), 7.07 (s, 1H), 8.30 (s, 1H), 8.53 (s, 1H), 10.15 (s, 1H).

Workup

  1. temperatureThe solution was cooled
  2. concentrationconcentrated
  3. customto give the hydrolyzed product as a yellow salt
  4. stirringThe reaction stirred at 50° C. for 2 hours
  5. temperatureThe solution was cooled
  6. extractionextracted with EtOAc
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-08f094cf40a746109e3218cf24ae7902
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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