Dimethylformamide → (S)-N-(5-(cyclopropylmethylthio)-3-(2-methylpyridin-3-yloxy)-pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine

HRID 534019Notes

Reaction equation

HRID 534019 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](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.[CH3:38]C([O-])(C)C.[K+].BrCC1CC1.CN(C=O)C>C1COCC1.CCOC(C)=O>[CH:25]1([CH2:24][S:23][C:20]2[CH:19]=[C:18]([O:30][C:31]3[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=3)[C:17]([NH:16][C:14]3[S:13][N:12]=[C:11]([C@H:2]4[CH2:3][O:4][C:5]5([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]5)[O:1]4)[N:15]=3)=[N:22][CH:21]=2)[CH2:38][CH2:26]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81503BromomethylcyclopropaneHCID 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 68481823(S)-N-(5-(cyclopropylmethylthio)-3-(2-methylpyridin-3-yloxy)-pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amineYield 74.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

to a solution of (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)propanate (0.428 g, 0.787 mmol) in THF (20 mL) was added potassium 2-methylpropan-2-olate (1M in THF, 236 ml, 2.36 mmol) and the reaction was stirred at ambient temperature for 5 minutes. (Bromomethyl)cyclopropane (0.106 g, 0.787 mmol) was added followed by DMF (5 mL) and the reaction was stirred for 1 hour at ambient temperature. The reaction was poured into EtOAc (500 mL) and the organic layer was washed with a 1:1 solution of water, 1N NaOH (100 mL total) and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified over silica get (40% EtOAc/CH2Cl2) to afford (S)-N-(5-(cyclopropylmethylthio)-3-(2-methylpyridin-3-yloxy)-pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine (0.30 g, 0.586 mmol, 74.5% yield).

Workup

  1. stirringthe reaction was stirred for 1 hour at ambient temperature
  2. washthe organic layer was washed with a 1:1 solution of water, 1N NaOH (100 mL total) and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified over silica
  6. customget (40% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-db1b380e2a7244c98f79c8473303e67a
Source dataset
uspto-grants-2014_10
Patent number
US08853409B2

Reaction notes

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