1-Methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione → (S)-1-(6-Fluoropyridin-3-ylmethyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione

HRID 2191236Notes

Reaction equation

HRID 2191236 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([N:14]3[CH2:18][CH2:17]C[C@H:15]3[CH2:19][O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[C:4](=[O:27])[C:3]1=[O:28].O(C[C@@H]1CCN1S(C1C=C2C(=CC=1)NC(=O)C2=O)(=O)=O)C1C=CC=CC=1.BrC[C:57]1[CH:58]=[CH:59][C:60]([F:63])=[N:61][CH:62]=1>>[F:63][C:60]1[N:61]=[CH:62][C:57]([CH2:1][N:2]2[C:10]3[C:5](=[CH:6][C:7]([S:11]([N:14]4[CH2:18][CH2:17][C@H:15]4[CH2:19][O:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)(=[O:13])=[O:12])=[CH:8][CH:9]=3)[C:4](=[O:27])[C:3]2=[O:28])=[CH:58][CH:59]=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 220506385-(Bromomethyl)-2-fluoropyridine

Product 1

HCID 11619968(S)-1-(6-Fluoropyridin-3-ylmethyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dioneYield 62%

Procedure

(S)-1-(6-Fluoropyridin-3-ylmethyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione (18g) was prepared according to the same procedure for compound 11a, except using compound 17 and 5-(bromomethyl)-2-fluoropyridine, and purified with ether to afford 74 mg (62%) of 18g as an orange solid, mp 176.8-178.3° C. 1H NMR (300 MHz, CDCl3) δ 8.27 (d, J=2.4 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 8.01 (dd, J=8.25 Hz, J=2.1 Hz, 1H), 7.79 (td, J=8.1 Hz, J=2.4 Hz, 1H), 7.22 (m, 2H), 7.00-6.77 (m, 5H), 4.92 (s, 2H), 4.49 (m, 1H), 4.09 (m, 2H), 3.85 (m, 2H), 2.35-2.23 (m, 2H). Anal. Calcd for C24H20FN3O5S: C, 59.87, H, 4.19; N, 8.73. Found: C, 59.81, H, 4.16; N, 8.62.

Workup

  1. custom(S)-1-(6-Fluoropyridin-3-ylmethyl)-5-(2-phenoxymethylazetidine-1-sulfonyl)-1H-indole-2,3-dione (18g) was prepared
  2. custompurified with ether

Sources & evidence

ORD record
ord-a97e26593e584b688f3aee0a50873d50
Source dataset
uspto-grants-2012_12
Patent number
US08329686B2

Reaction notes

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