1-Methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione → (S)-1-(2-Fluoropyridin-4-yl-methyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione

HRID 2191237Notes

Reaction equation

HRID 2191237 reaction equation
CN1C2C(=CC(S(N3CCC[C@H]3COC3C=CC=CC=3)(=O)=O)=CC=2)C(=O)C1=O.[O:29]([CH2:36][C@@H:37]1[CH2:40][CH2:39][N:38]1[S:41]([C:44]1[CH:45]=[C:46]2[C:50](=[CH:51][CH:52]=1)[NH:49][C:48](=[O:53])[C:47]2=[O:54])(=[O:43])=[O:42])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.Br[CH2:56][C:57]1[CH:62]=[CH:61][N:60]=[C:59]([F:63])[CH:58]=1>>[F:63][C:59]1[CH:58]=[C:57]([CH2:56][N:49]2[C:50]3[C:46](=[CH:45][C:44]([S:41]([N:38]4[CH2:39][CH2:40][C@H:37]4[CH2:36][O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)(=[O:43])=[O:42])=[CH:52][CH:51]=3)[C:47](=[O:54])[C:48]2=[O:53])[CH:62]=[CH:61][N:60]=1

Participants

4

Reactant 3

HCID 52888501-Methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dioneHCID 11624920(S)-5-(2-phenoxymethyl-azetidine-1-sulfonyl)-1H-indole-2,3-dioneHCID 139851684-Bromomethyl-2-fluoropyridine

Product 1

HCID 11576622(S)-1-(2-Fluoropyridin-4-yl-methyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dioneYield 30%

Procedure

(S)-1-(2-Fluoropyridin-4-yl-methyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione (18h) was prepared according to the same procedure for compound 11a, except using compound 17 and 4-(bromomethyl)-2-fluoropyridine, and purified with ether to afford 36 mg (30%) of 18h as an orange solid, mp 159.0-159.9° C. 1H NMR (300 MHz, CDCl3) δ 8.23 (d, J=5.1 Hz, 1H), 8.08 (s, 1. H), 7.98 (dd, J=8.7 Hz, J=2.1 Hz, 1H), 7.22 (m, 2H), 7.10 (d, J=5.4 Hz, 1H), 6.93 (t, J=7.5 Hz, 1H), 6.84-6.72 (m, 4H), 4.93 (s, 2H), 4.49 (m, 1H), 4.07 (m, 2H), 3.91-3.81 (m, 2H), 2.35-2.22 (m, 2H). Anal. Calcd for C24.FN3O5S.0.5H2O: C, 58.77, H, 4.32; N, 8.57. Found: C, 58.69, H, 4.45; N, 8.26.

Workup

  1. custom(S)-1-(2-Fluoropyridin-4-yl-methyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione (18h) was prepared
  2. custompurified with ether

Sources & evidence

ORD record
ord-40373a94462642aa903b848e25cbca9f
Source dataset
uspto-grants-2012_12
Patent number
US08329686B2

Reaction notes

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