Ammonia → HCID 68579792, compound

HRID 2047322Notes

Reaction equation

HRID 2047322 reaction equation
[CH3:1][N:2]([CH3:31])[C:3]1[CH:8]=[C:7]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:25]=[C:24]([CH3:26])[C:17]([O:18][CH2:19][CH:20]([OH:23])[CH2:21]O)=[C:16]([CH2:27][CH3:28])[CH:15]=3)[N:10]=2)[CH:6]=[C:5]([CH2:29][CH3:30])[N:4]=1.CC[N:34](C(C)C)C(C)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.N>C1COCC1.CO>[NH2:34][CH2:21][CH:20]([OH:23])[CH2:19][O:18][C:17]1[C:24]([CH3:26])=[CH:25][C:14]([C:11]2[N:10]=[C:9]([C:7]3[CH:6]=[C:5]([CH2:29][CH3:30])[N:4]=[C:3]([N:2]([CH3:31])[CH3:1])[CH:8]=3)[O:13][N:12]=2)=[CH:15][C:16]=1[CH2:27][CH3:28]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85257MethanesulfonateHCID 68577688HCID 68577688, compound

Product 1

HCID 68579792HCID 68579792, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of rac-3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol (78 mg, 0.183 mmol) and DIPEA (47 mg, 0.365 mmol) in THF (5 mL) is added methanesulfonylchloride (23 mg, 0.201 mmol) at 0° C. The mixture is stirred at 0° C. for 3 h (Mesylate: LC-MS: tR=0.88 min; [M+1]+=505.12) before it is added to 7 N NH3 in methanol (10 mL). The mixture is stirred at 65° C. for 16 h. The solvent is removed in vacuo and the crude product is purified on prep. TLC plates with DCM containing 5% of methanol and 10% of 7 N NH3 in methanol to give rac-1-amino-3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phen-oxy}-propan-2-ol as a yellow resin. This material is dissolved in DCM and to the solution glycolic acid (29 mg, 0.375 mmol) and DIPEA (70 mg, 0.540 mmol) is added. The mixture is cooled to 0° C. before TBTU (71 mg, 0.221 mmol) is added. The mixture is stirred at 0° C. for 1 h before it is diluted with EA (100 mL), washed twice with sat. aq. NaHCO3-solution (25 mL), dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC plates with heptane:EA 7:3 to give rac-N-(3-{4-[5-(2-dimethylamino-6-ethyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide (32 mg) as a yellow resin; LC-MS: tR=0.76 min; [M+1]+=484.19.

Workup

  1. customThe solvent is removed in vacuo
  2. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-85e6b7307f6a4db2a7cb26d46bd878b6
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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