Methanesulfonamide → 5-Cyclopropyl-N-(cyclopropylsulfonyl)-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzamide

HRID 1849703Notes

Reaction equation

HRID 1849703 reaction equation
C12(COC3C(C4CC4)=CC(C(O)=O)=CN=3)CC3CC(CC(C3)C1)C2.[CH:25]1([C:28]2[C:29]([O:38][CH2:39][C:40]34[CH2:50][C:44]5([F:51])[CH2:45][C:46]([F:49])([CH2:48][C:42]([F:52])([CH2:43]5)[CH2:41]3)[CH2:47]4)=[CH:30][C:31]([F:37])=[C:32]([CH:36]=2)[C:33]([OH:35])=O)[CH2:27][CH2:26]1.CS(N)(=O)=O.[CH:58]1([S:61]([NH2:64])(=[O:63])=[O:62])[CH2:60][CH2:59]1>>[CH:25]1([C:28]2[C:29]([O:38][CH2:39][C:40]34[CH2:50][C:44]5([F:51])[CH2:43][C:42]([F:52])([CH2:48][C:46]([F:49])([CH2:45]5)[CH2:47]3)[CH2:41]4)=[CH:30][C:31]([F:37])=[C:32]([CH:36]=2)[C:33]([NH:64][S:61]([CH:58]2[CH2:60][CH2:59]2)(=[O:63])=[O:62])=[O:35])[CH2:26][CH2:27]1

Participants

5

Reactant 4

HCID 72879MethanesulfonamideHCID 15765418CyclopropanesulfonamideHCID 867029246-(Adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acidHCID 867035735-Cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid

Product 1

HCID 867035755-Cyclopropyl-N-(cyclopropylsulfonyl)-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzamideYield 79%

Procedure

Following the procedure as described in Example 150 step 5 and making variations as required to replace 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acid with 5-cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid and to replace methyl sulfonamide with cyclopropanesulfonamide. Purification by silica gel column chromatography (1:1 hexanes:ethyl acetate (+0.2% acetic acid v/v)) gave the title compound as a colorless solid (0.10 g, 79%): 1H NMR (300 MHz, DMSO-d6) δ 11.82 (br s, 1H), 7.12 (d, J=8.33 Hz, 1H), 6.94 (d, J=12.86 Hz, 1H), 3.93 (s, 2H), 3.09-2.99 (m, 1H), 2.25-2.13 (m, 3H), 2.10-1.98 (m, 4H), 1.85-1.75 (m, 6H), 1.12-1.01 (m, 4H), 0.93-0.84 (m, 2H), 0.66-0.59 (m, 2H); MS (ES+) m/z 502.1 (M+1).

Workup

  1. customPurification by silica gel column chromatography (1:1 hexanes

Sources & evidence

ORD record
ord-f7ac4ea00a624d9f83b2e961cdf9f8ef
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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