2-(Bromomethyl)-1,4-difluorobenzene → HCID 71209167, compound

HRID 1912579Notes

Reaction equation

HRID 1912579 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].Br[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[F:40]>>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 5228302-(Bromomethyl)-1,4-difluorobenzeneHCID 71209221HCID 71209221, compound

Product 2

HCID 71209167HCID 71209167, compoundHCID 71209492HCID 71209492, compound

Procedure

The title compound was prepared in a manner similar to that described in Example 27 from (S)-methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 2-(bromomethyl)-1,4-difluorobenzene, except that the racemic mixture obtained in Step G was purified by preparative HPLC using an IC column (250 mm×30 mm I.D.; 5 um) from Chiral Technologies (West Chester, Pa., USA). The mobile phase was comprised of 80% hexanes containing 0.1% formic acid (v/v) and 20% isopropanol, operating at 42.5 ml/min, with triggered collections at 280 nm (Rt=6.80 minutes) to give to give (S)-2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetic acid. (S)-2-(Tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetic acid was then used as in Example 27, Step H to afford the title compound. 1H NMR (400 MHz, CHLOROFORM-d) d=7.50-7.41 (m, 1 H), 7.23-7.17 (m, 1 H), 7.14 (t, J=3.4 Hz, 1 H), 7.06 (td, J=4.5, 9.3 Hz, 1 H), 7.01-6.92 (m, 3 H), 6.32 (dd, J=3.5, 11.3 Hz, 1 H), 5.64-5.53 (m, 3 H), 4.29 (t, J=4.6 Hz, 2 H), 2.96-2.80 (m, 2 H), 2.79 (s, 3 H), 2.09 (d, J=5.3 Hz, 2 H), 1.03-0.90 (s, 9 H).

Workup

  1. customwas purified by preparative HPLC
  2. customto give

Sources & evidence

ORD record
ord-749f5ace6e5a40c6bf83734f64dddd54
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

Loading…