2-Bromoethyl methyl ether → (S)-N-(5-(2-methoxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1523630Notes

Reaction equation

HRID 1523630 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)[O:4][CH2:3][C@@H:2]1[C:11]1[N:15]=[C:14]([NH:16][C:17]2[N:22]=[CH:21][C:20]([S:23][CH2:24][CH2:25]C(OC)=O)=[CH:19][C:18]=2[O:30][C:31]2[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=2)[S:13][N:12]=1.C[C:39]([O-:42])(C)C.[K+].BrCCOC>C1COCC1>[CH3:39][O:42][CH2:25][CH2:24][S:23][C:20]1[CH:19]=[C:18]([O:30][C:31]2[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=2)[C:17]([NH:16][C:14]2[S:13][N:12]=[C:11]([C@H:2]3[CH2:3][O:4][C:5]4([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]4)[O:1]3)[N:15]=2)=[N:22][CH:21]=1

Participants

5

Reactant 3

HCID 809722-Bromoethyl methyl etherHCID 23665647Potassium tert-butoxideHCID 67487943(S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate

Product 1

HCID 67487217(S)-N-(5-(2-methoxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amineYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-Methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate (2.0 g, 3.68 mmol) was dissolved in THF (20 mL) and nitrogen was bubbled through the solution for 5 minutes. Potassium 2-methylpropan-2-olate (1M in THF, 11.0 ml, 11.0 mmol) was added and the reaction was stirred at ambient temperature for 1 minute. 1-Bromo-2-methoxyethane (0.518 ml, 5.52 mmol) was added and the reaction was stirred at ambient temperature for 20 minutes. The reaction was partitioned between EtOAc and aqueous NH4Cl, dried, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)—N-(5-(2-methoxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.9 g, 3.68 mmol, 100% yield).

Workup

  1. customnitrogen was bubbled through the solution for 5 minutes
  2. stirringthe reaction was stirred at ambient temperature for 20 minutes
  3. customThe reaction was partitioned between EtOAc and aqueous NH4Cl
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-0c660f3485f54473b19574acf737ed14
Source dataset
uspto-grants-2015_07
Patent number
US09079890B2

Reaction notes

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