4-Toluenesulfonyl chloride → [5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1921377Notes

Reaction equation

HRID 1921377 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]([NH:11][NH:12][C:13]([C:15]1[CH:20]=[C:19]([CH2:21][CH3:22])[C:18](=[O:23])[NH:17][C:16]=1[CH3:24])=[O:14])=O)([CH3:4])([CH3:3])[CH3:2].S(Cl)([C:29]1C=CC(C)=CC=1)(=O)=O.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>O1CCCC1>[C:1]([O:5][C:6](=[O:25])[NH:7][CH2:8][C:9]1[O:14][C:13]([C:15]2[C:16]([CH3:24])=[N:17][C:18]([O:23][CH3:29])=[C:19]([CH2:21][CH3:22])[CH:20]=2)=[N:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 67492289{2-[N'-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl)-hydrazino]-2-oxo-ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 67492424[5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl esterYield 182%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
145 °C

Procedure

Into each of three microwave vials is added {2-[N′-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl)-hydrazino]-2-oxo-ethyl}-carbamic acid tert-butyl ester (190 mg, 0.519 mmol), tosyl chloride (119 mg, 0.624 mmol), and 2-t-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol/g, 1.18 g, 2.6 mmol) and anhydrous tetrahydrofuran (6 mL). Each vial is flushed with nitrogen, sealed and heated in the CEM Discover microwave at 145° C. holding at that temperature for 3 min, with a maximum pressure of 7.3 bar. LC/MS shows the reaction is complete. The product from all three vials are filtered and washed with THF. The filtrate is evaporated, and the residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1). Fractions containing the product are combined again and evaporated to give [5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester (329 mg, 61% yield). MS: m/e 719 (95%) (2M+Na), 249 (100%) (M+H); 1H NMR (CDCl3, δ, ppm): 7.87 (1H, s), 5.15 (1H, br.), 4.61 (2H, br.d), 4.00 (3H, s), 2.79 (3H, s), 2.60 (2H, q), 1.49 (9H, s), 1.21 (3H, t).

Workup

  1. customEach vial is flushed with nitrogen
  2. customsealed
  3. filtrationThe product from all three vials are filtered
  4. washwashed with THF
  5. customThe filtrate is evaporated
  6. customthe residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1)
  7. additionFractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-ef2f4218ab4c452e903911df716eb4d3
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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