Hydrochloric Acid → (S)-3-(2-Ethyl-4-{5-[6-(1-ethyl-propyl)-4-methyl-pyridin-2-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-propane-1,2-diol

HRID 2037382Notes

Reaction equation

HRID 2037382 reaction equation
[CH2:1]([CH:3]([C:6]1[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[C:8]([CH3:15])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[CH3:16][C:17]1([CH3:37])[O:21][C@H:20]([CH2:22][O:23][C:24]2[C:33]([CH3:34])=[CH:32][C:27]([C:28]([NH:30][OH:31])=[NH:29])=[CH:26][C:25]=2[CH2:35][CH3:36])[CH2:19][O:18]1.Cl>O1CCOCC1>[CH3:16][C:17]1([CH3:37])[O:21][C@H:20]([CH2:22][O:23][C:24]2[C:33]([CH3:34])=[CH:32][C:27]([C:28]3[N:30]=[C:12]([C:10]4[CH:9]=[C:8]([CH3:15])[CH:7]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[N:11]=4)[O:14][N:29]=3)=[CH:26][C:25]=2[CH2:35][CH3:36])[CH2:19][O:18]1.[CH2:35]([C:25]1[CH:26]=[C:27]([C:28]2[N:29]=[C:12]([C:10]3[CH:9]=[C:8]([CH3:15])[CH:7]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[N:11]=3)[O:31][N:30]=2)[CH:32]=[C:33]([CH3:34])[C:24]=1[O:23][CH2:22][C@@H:20]([OH:21])[CH2:19][OH:18])[CH3:36]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 686301606-(1-Ethyl-propyl)-4-methyl-pyridine-2-carboxylic acidHCID 178436628HCID 178436628, compound

Product 2

HCID 44218321(S)-3-(2-Ethyl-4-{5-[6-(1-ethyl-propyl)-4-methyl-pyridin-2-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-propane-1,2-diolHCID 686310692-{(R)-3-[4-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-6-(1-ethyl-propyl)-4-methyl-pyridine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-{(R)-3-[4-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-6-(1-ethyl-propyl)-4-methyl-pyridine (42 mg) is prepared by coupling and cyclizing 6-(1-ethyl-propyl)-4-methyl-pyridine-2-carboxylic acid (67 mg, 323 μmol) with (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-N-hydroxy-5-methyl-benzamidine (130 mg, 420 μmol) as described in Example 1. This material is dissolved in dioxane (5 mL) and 2 M aq. HCl (1 mL) and the mixture is stirred at rt for 16 h. The mixture is concentrated and the crude product is purified on prep. TLC using DCM containing 10% of 7 N NH3 in methanol to give the title compound (25 mg) as a pale yellow glass; LC-MS**: tR=0.80 min, [M+H]+=440.27; 1H NMR (CDCl3): δ0.85 (t, J=7.3 Hz, 6H), 1.32 (t, J=7.3 Hz, 3H), 1.79 (quint, J=7.3 Hz, 4H), 2.40 (s, 3H), 2.49 (s, 3H), 2.72-2.83 (m, 4H), 3.82-4.00 (m, 5H), 4.13-4.21 (m, 1H), 7.16 (s, 1H), 7.91 (s, 1H), 7.92 (s, 1H), 8.00 (s, 1H).

Workup

  1. concentrationThe mixture is concentrated
  2. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-c711307654e84b11aa604befd4077470
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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