Methanesulfonamide → N-(Azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzamide

HRID 1849702Notes

Reaction equation

HRID 1849702 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](O)=[O:34])[CH2:27][CH2:26]1.CS(N)(=O)=O.[N:58]1([S:62]([NH2:65])(=[O:64])=[O:63])[CH2:61][CH2:60][CH2:59]1>>[N:58]1([S:62]([NH:65][C:33](=[O:34])[C:32]2[CH:36]=[C:28]([CH:25]3[CH2:26][CH2:27]3)[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]=2[F:37])(=[O:64])=[O:63])[CH2:61][CH2:60][CH2:59]1

Participants

5

Reactant 4

HCID 72879MethanesulfonamideHCID 450805661-AzetidinesulfonamideHCID 867029246-(Adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acidHCID 867035735-Cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid

Product 1

HCID 86703574N-(Azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzamideYield 47%

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 azetidine-1-sulfonamide. 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, 47%): 1H NMR (300 MHz, DMSO-d6) δ 11.61 (br s, 1H), 7.14 (d, J=8.3 Hz, 1H), 6.94 (d, J=12.7 Hz, 1H), 4.01 (t, J=7.6 Hz, 4H), 3.93 (s, 2H), 2.25-1.99 (m, 9H), 1.80 (s, 6H), 0.93-0.85 (m, 2H), 0.67-0.60 (m, 2H); MS (ES−) m/z 515.1 (M−1).

Workup

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

Sources & evidence

ORD record
ord-81a688d79b0a422e8b297f02384dfae3
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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