tert-butyl {2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenyl piperidin-1-yl)carbonyl]phenyl}sulfonylcarbamate → 4-chloro-2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-aza bicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]-N-propylbenzenesulfonamide

HRID 1992127Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:11]([NH:14][CH2:15][CH2:16][CH3:17])(=[O:13])=[O:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.ClC1C=C(C=CC=1S(NCCC)(=O)=O)C(O)=O.Cl.Cl.[CH3:37][C:38]1[N:42]([CH:43]2[CH2:49][CH:48]3[N:50]([CH2:51][CH2:52][C:53]4([C:59]5[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=5)[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]4)[CH:45]([CH2:46][CH2:47]3)[CH2:44]2)[C:41]2[CH:65]=[CH:66][CH:67]=[CH:68][C:40]=2[N:39]=1.CC1N(C2CC3N(CCC4(C5C=CC=CC=5)CCN(C(C5C=CC=CC=5S(NC(=O)OC(C)(C)C)(=O)=O)=O)CC4)C(CC3)C2)C2C=CC=CC=2N=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:11]([NH:14][CH2:15][CH2:16][CH3:17])(=[O:13])=[O:12])=[C:6]([C:7]([N:56]2[CH2:55][CH2:54][C:53]([CH2:52][CH2:51][N:50]3[CH:45]4[CH2:46][CH2:47][CH:48]3[CH2:49][CH:43]([N:42]3[C:41]5[CH:65]=[CH:66][CH:67]=[CH:68][C:40]=5[N:39]=[C:38]3[CH3:37])[CH2:44]4)([C:59]3[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=3)[CH2:58][CH2:57]2)=[O:9])[CH:10]=1

Participants

Reactant 4

HCID 58728709tert-butyl {2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenyl piperidin-1-yl)carbonyl]phenyl}sulfonylcarbamate

HCID 686757782-methyl-1-{8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride

HCID 686764733-Chloro-4-(propylsulfamoyl)benzoic acid

HCID 686771555-Chloro-2-[(propylamino) sulfonyl]benzoic acid

Product 1

HCID 587288264-chloro-2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-aza bicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]-N-propylbenzenesulfonamideYield 11%

Procedure

The title compound was prepared from a mixture of 5-chloro-2-[(propylamino) sulfonyl]benzoic acid and 3-chloro-4-[(propylamino) sulfonyl]benzoic acid 2e and endo 2-methyl-1-(8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl)-1H-benzimidazole dihydrochloride II following the general procedure for tert-butyl {2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]phenyl}sulfonylcarbamate 1c. The desired regioisomer was purified by column chromatography on silica gel eluting with 10% methanol in ethyl acetate to afford 4-chloro-2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-aza bicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]-N-propylbenzenesulfonamide 5 as a white solid (15 mg, 11% yield). 1H NMR (400 MHz, CDCl3) δ (8.12, 1H, J=8.0 Hz), 7.65 (m, 1H), 7.52 (m, 1H), 7.41-7.12 (m, 9H), 5.10 (t, 1H, J=6.0 Hz), 4.59 (m, 1H), 4.20 (m, 1H), 3.48-3.19 (m, 6H), 2.89 (q, 1H, J=6.6 Hz), 2.56 (s, 3H), 2.55-2.32 (m, 3H), 2.17 (m, 1H), 1.93-1.64 (m, 10H), 1.61 (m, 1H), 1.50 (m, 2H), 0.882 (t, 3H, J=7.3 Hz). ES-LCMS m/z 690.33 (M+2H). Analytical HPLC (Method Y) Rt 5.39 (93.34%).

Workup

customThe desired regioisomer was purified by column chromatography on silica gel eluting with 10% methanol in ethyl acetate

Sources & evidence

ORD record: ord-2d15b0f52acf4cc2b9471901c54039da
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07645771B2

Reaction notes

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