Toluene → HCID 67189504, compound

HRID 546244Notes

Reaction equation

[C:1](=[O:4])([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:18]([CH2:32][CH:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)[C:19]([NH:21][C:22]2[CH:26]=[CH:25][N:24]([CH2:27]C=C(C)C)[N:23]=2)=[O:20])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:17])(=[O:16])=[O:15].CS(N)(=O)=O.S([O-])([O-])=[O:44].[Na+].[Na+].[C:49]1([CH3:55])C=CC=C[CH:50]=1>[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[Os](=O)(=O)(=O)=O.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.O.C(OCC)(=O)C.O.C(O)(C)(C)C>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:18]([CH2:32][CH:33]2[CH2:34][CH2:35][CH2:36][CH2:37]2)[C:19]([NH:21][C:22]2[CH:26]=[CH:25][N:24]([CH2:27][CH:1]([OH:4])[C:49]([OH:44])([CH3:55])[CH3:50])[N:23]=2)=[O:20])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:17])(=[O:16])=[O:15]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of potassium ferricyanide (21 mg, 0.06 mmol), potassium carbonate (8.9 mg, 0.06 mmol), and (DHQ)2PHAL (0.3 mg, 3%) was treated with a solution of water/tert-butyl alcohol (5 mL, 1:1) and stirred at 25° C. for 5 min (until clear solution obtained). The reaction mixture was treated with a 0.2 M solution of osmium tetroxide in toluene (1μ, 1%) and cooled to 0° C. To this was added 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-methyl-but-2-enyl)-1H-pyrazol-3-yl]-propionamide (prepared as in Example 51, 10 mg, 0.022 mmol) and methane sulfonamide (2 mg, 0.02 mmol). The heterogeneous mixture was stirred at 0° C. for 20 h. After such time the cooling bath was removed and the mixture was treated while stirring with ethyl acetate (15 mL) and sodium sulfite (50 mg, 0.39 mmol). To this solution was added water (20 mL) and the phases were separated. The aqueous phase was backextracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification an AnaLogix Intelliflash system (4 g column, 70% ethyl acetate/hexanes to 100% ethyl acetate) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2,3-dihydroxy-3-methyl-butyl)-1H-pyrazol-3yl]propionamide (6.7 mg, 63%) as a single diastereomer of unknown stereochemistry at the hydroxyl carbon center: [α]29589=−10.2° (c=0.48, methanol); ES-HRMS m/e calcd for C23H32ClN3O5S (M+H)+ 498.1824, observed 498.1824; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.05 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.11 (m, 2H, CH2) 1.39-1.79 (m, 8H, 4×CH2), 2.10 (m, 1H, CH), 3.34 (s, 3H, SO2CH3), 3.46 (m, 1H, OCH), 3.75 (dd, J=9.6 Hz, 13.5 Hz, 1H, NCH of NCH2), 3.90 (m, 1H, ArCHCO), 4.21 (d, J=13.5 Hz, 1H, NCH of NCH2), 4.42 (s, 1H, OH), 4.82 (d, J=6.3 Hz, 1H, OH), 6.39 (d, J=2.3 Hz, 1H, Ar), 7.51 (d, J=2.3 Hz, 1H, Ar), 7.59 (dd, Jo=8.3, Jm=1.6 Hz, 1H, Ar), 7.70 (d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.3 Hz, 1H, Ar), 10.78 (s, 1H, NH).

Workup

custom(until clear solution obtained)
temperaturecooled to 0° C
stirringThe heterogeneous mixture was stirred at 0° C. for 20 h
customAfter such time the cooling bath was removed
additionthe mixture was treated
customthe phases were separated
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customPurification an AnaLogix Intelliflash system (4 g column, 70% ethyl acetate/hexanes to 100% ethyl acetate)

Sources & evidence

ORD record: ord-95a3eea5cc7a410e90f4807db6009252
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07935699B2

Reaction notes

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