Acetone → HCID 68747463, compound

HRID 333302Notes

Reaction equation

[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:15][C:16]([C:18]2(CC(Cl)=C)[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[C:9]2[N:13]([CH3:14])[N:12]=[N:11][N:10]=2)=[CH:3][CH:2]=1.[C:33]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:38]=[CH:37][C:36]([CH2:39][C@H:40]([NH:47][C:48]([C:50]2(CC(Cl)=C)[CH2:54][CH2:53][CH2:52][CH2:51]2)=[O:49])[C:41]2[N:42]=[N:43][N:44]([CH3:46])[N:45]=2)=[CH:35][CH:34]=1.C[C:66]([CH3:68])=[O:67]>>[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:15][C:16]([C:18]2([CH2:68][C:66]([OH:49])=[O:67])[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[C:9]2[N:13]([CH3:14])[N:12]=[N:11][N:10]=2)=[CH:3][CH:2]=1.[C:33]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:38]=[CH:37][C:36]([CH2:39][C@H:40]([NH:47][C:48]([C:50]2([CH2:68][C:66]([OH:17])=[O:67])[CH2:54][CH2:53][CH2:52][CH2:51]2)=[O:49])[C:41]2[N:42]=[N:43][N:44]([CH3:46])[N:45]=2)=[CH:35][CH:34]=1

Participants

Reactant 3

HCID 180Acetone

HCID 87560039HCID 87560039, compound

HCID 87560810HCID 87560810, compound

Product 2

HCID 68747463HCID 68747463, compound

HCID 68749382HCID 68749382, compound

Conditions

Temperature: -78 °C

Procedure

To a mixture of (S)—N-(2-(biphenyl-4-yl)-1-(1-methyl-1H-tetrazol-5-yl)ethyl)-1-(2-chloroallyl)cyclopentanecarboxamide and (S)—N-(2-(biphenyl-4-yl)-1-(2-methyl-2H-tetrazol-5-yl)ethyl)-1-(2-chloroallyl)cyclopentanecarboxamide in acetone at −7° C. was bubbled ozone for 30 seconds using ozone generator. The mixture became a persistent pale blue color. The mixture was stirred at −78° C. for 1 minute. To the mixture was bubbled oxygen gas for 10 minutes and was added dimethyl sulfide (0.5 mL) followed by water (1 mL). The cooling bath was removed and stirred for 1 hour at room temperature. The mixture was concentrated under reduced pressure and diluted in EtOAc. The mixture was acidified with 1 M HCl until pH=1. The organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN gradient) to give two isomers, (S)-2-(1-(2-(biphenyl-4-yl)-1-(1-methyl-1H-tetrazol-5-yl)ethylcarbamoyl)cyclopentyl)acetic acid and (S)-2-(1-(2-(biphenyl-4-yl)-1-(2-methyl-2H-tetrazol-5-yl)ethylcarbamoyl)cyclopentyl)acetic acid (11 mg, regioisomer 1, 7.6 mg regioisomer 2). Regioisomer 1: HPLC retention time=1.57 minutes (condition D); MS (m+1)=434.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.57-1.85 (m, 6H), 1.89-2.19 (m, 2H), 2.73 (q, J=16.4 Hz, 2H), 3.18-3.41 (m, 1H), 3.48 (dd, J=13.3, 6.4 Hz, 1H), 3.69 (s, 3H), 5.42-5.65 (m, 1H), 7.03 (br. s., 1H), 7.08-7.24 (m, 2H), 7.34-7.41 (m, 1H), 7.42-7.65 (m, 6H). Regioisomer 2: HPLC retention time=1.66 minutes (condition D); MS (m+1)=434.3. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44-1.73 (m, 6H), 1.73-1.99 (m, 2H), 2.59 (s, 2H), 3.15-3.38 (m, 2H), 4.24 (s, 3H), 5.50-5.79 (m, 1H), 6.60 (br. s., 1H), 7.06 (d, J=8.1 Hz, 2H), 7.19 (s, 2H), 7.22-7.30 (m, 1H), 7.30-7.56 (m, 4H).

Workup

customwas bubbled ozone for 30 seconds
customTo the mixture was bubbled oxygen gas for 10 minutes
additionwas added dimethyl sulfide (0.5 mL)
customThe cooling bath was removed
stirringstirred for 1 hour at room temperature
concentrationThe mixture was concentrated under reduced pressure
additiondiluted in EtOAc
washThe organic layer was washed with water, brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN gradient)

Sources & evidence

ORD record: ord-5f636a09b01a47d5afa9a1b1735c83d9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877815B2

Reaction notes

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