Methanol → N-[4-(4-chloro-5-formyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamide

HRID 2282294Notes

Reaction equation

HRID 2282294 reaction equation
Cl[C:2]1[S:3][C:4]([CH:8]=[O:9])=[C:5]([Cl:7])[N:6]=1.C[Sn](C)(C)[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19](=[O:21])[CH3:20])[CH:13]=1.[Cl-].[Li+].CO>O1CCOCC1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:7][C:5]1[N:6]=[C:2]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19](=[O:21])[CH3:20])[CH:13]=2)[S:3][C:4]=1[CH:8]=[O:9]

Participants

8

Reactant 4

HCID 887MethanolHCID 433294Lithium ChlorideHCID 14886722,4-Dichloro-1,3-thiazole-5-carboxaldehydeHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamide

Product 1

HCID 86649613N-[4-(4-chloro-5-formyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamideYield 46%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

2,4-Dichloro-5-thiazolecarboxaldehyde (2.50 g, 0.0137 mol), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (4.93 g, 0.0165 mol), lithium chloride (1.75 g, 0.0412 mol), copper(I) iodide (0.785 g, 0.00412 mol), tetrakis(triphenylphosphine)palladium(0) (0.794 g, 0.000687 mol) were combined in dioxane (200 mL) under an atmosphere of Argon. The solution was heated at 110° C. for 2 hr. TLC indicated complete conversion. Mixture was cooled to rt and MeOH (100 mL) was added until almost all solids dissolved. Suspension was filtered through celite and the filtrate was evaporated. Water (100 mL) was added and the solids were collected by filtration, washed with water and hexane and dried in vacuum at 40° C. to give 1.76 g of amorphous solid (46%). LCMS: (FA) ES+ 282, 284. 1H NMR (400 MHz, d6-DMSO) 10.83 (s, 1H), 10.02 (s, 1H), 8.70 (s, 1H), 8.51 (dd, J=5.20, 0.67 Hz, 1H), 7.68 (dd, J=5.20, 1.67 Hz, 1H), 2.13 (s, 3H).

Workup

  1. temperatureMixture was cooled to rt
  2. dissolutiondissolved
  3. filtrationSuspension was filtered through celite
  4. customthe filtrate was evaporated
  5. additionWater (100 mL) was added
  6. filtrationthe solids were collected by filtration
  7. washwashed with water and hexane
  8. customdried in vacuum at 40° C.

Sources & evidence

ORD record
ord-28cc748ce43e417cb70056b089778513
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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