Methanesulfonic Acid → HCID 46852285, compound

HRID 1258126Notes

Reaction equation

HRID 1258126 reaction equation
[F:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:27])[CH2:8][NH:9][C@@:10]2([CH3:26])[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]3[N:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[O:18][N:17]=3)[C:11]2([CH3:25])[CH3:24])[C@H:4]([C:28]#[N:29])[CH2:3]1.[CH3:30][S:31]([OH:34])(=[O:33])=[O:32]>C(OCC)(=O)C>[CH3:30][S:31]([OH:34])(=[O:33])=[O:32].[F:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:27])[CH2:8][NH:9][C@@:10]2([CH3:26])[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]3[N:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[O:18][N:17]=3)[C:11]2([CH3:24])[CH3:25])[C@H:4]([C:28]#[N:29])[CH2:3]1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 46852286HCID 46852286, compound

Product 1

HCID 46852285HCID 46852285, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred suspension of the step-2 intermediate (0.15 g, 0.52 mmol), K2CO3 (0.138 g, 1 mmol) and KI catalytic amount in 1 mL of DMSO was added a DMSO solution of intermediate 20 (0.98 g, 0.5 mmol) and the reaction mixture was stirred for 12 hours under nitrogen atmosphere. After completion of the reaction, it was diluted with ethyl acetate and water. The layers were separated and the aqueous layer was washed twice with ethyl acetate. The combined organic layers was dried over anhydrous Na2SO4, concentrated and purified by chromatography to yield (2S,4S)-4-fluoro-1-(2-((1S,3S)-3-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-1,2,2-trimethylcyclopentylamino)acetyl)pyrrolidine-2-carbonitrile. (2S,4S)-4-fluoro-1-(2-((1S,3S)-3-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-1,2,2-trimethylcyclopentylamino)acetyl)pyrrolidine-2-carbonitrile (0.032 g, 0.08 mmole) was dissolved in ethyl acetate and solution of methanesulphonic acid (7.9 mg, 0.08 mmole) in 1 mL ethyl acetate was added and stirred for one hour. Then ethyl acetate was concentrated and washed with diethyl ether to obtain the title compound. 0.03 g, Off white hygroscopic solid. 1H NMR (400 MHz, D2O) δ ppm: 1.02 (s, 3H), 1.09 (s, 3H), 1.35 (s, 3H), 1.37 (d, 6H), 1.49-1.57 (m, 1H), 1.84-1.89 (m, 2H), 2.04-2.08 (m, 1H), 2.35-2.38 (m, 1H), 2.40-2.75 (m, 3H), 2.80 (s, 3H), 2.9-2.94 (m, 1H), 3.26-3.29 (m, 1H), 3.77-3.80 (m, 1H), 3.90-3.95 (m, 1H), 4.01-4.15 (m, 1H), 4.20-4.35 (m, 1H), 5.10, d, J=9.36 Hz, 0.8H), 5.25 (d, J=9.36 Hz, 0.2H), 5.55 (d, J=51 Hz, 0.2H), 5.56 (d, J=51 Hz, 0.8H). m/z (M+H): 406.2.

Workup

  1. concentrationThen ethyl acetate was concentrated
  2. washwashed with diethyl ether

Sources & evidence

ORD record
ord-4af5bec2f0d24bbf955e29c247f40f72
Source dataset
uspto-grants-2013_06
Patent number
US08466145B2

Reaction notes

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