1-Bromo-3-methoxypropane → (S)-N-(5-(3-methoxypropylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

HRID 534034Notes

Reaction equation

HRID 534034 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:26]([O:28][CH3:29])=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.CC([O-])(C)C.[K+].BrCCCOC>C1COCC1.C(OCC)(=O)C>[CH3:29][O:28][CH2:26][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([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]4)[O:1]3)[N:15]=2)=[N:22][CH:21]=1

Participants

6

Reactant 3

HCID 5245511-Bromo-3-methoxypropaneHCID 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 68481884(S)-N-(5-(3-methoxypropylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amineYield 84.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-Methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate (105 mg, 0.19 mmol) was dissolved in THF (5 ml) and KOtBu (65 mg, 0.58 mmol) was added. The mixture was agitated for 30 minutes and 1-bromo-3-methoxypropane (37 mg, 0.24 mmol) was added. The mixture was agitated for 1hour, diluted with ethyl acetate, washed with sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified over silica gel (60-75% ethyl acetate/hexanes to afford (S)-N-(5-(3-methoxypropylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine (85 mg, 83% yield) as glassy colorless solid.

Workup

  1. stirringThe mixture was agitated for 1hour
  2. washwashed with sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified over silica gel (60-75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5b004a45af6f4189bfc139be90f3a45e
Source dataset
uspto-grants-2014_10
Patent number
US08853409B2

Reaction notes

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