1-(Bromomethyl)-2,3-difluoro-benzene → HCID 71209041, compound

HRID 1912578Notes

Reaction equation

HRID 1912578 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]=[CH:37][CH:36]=[C:35]([F:39])[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]=[CH:37][CH:36]=[C:35]([F:39])[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 5179841-(Bromomethyl)-2,3-difluoro-benzeneHCID 71209221HCID 71209221, compound

Product 2

HCID 71209041HCID 71209041, compoundHCID 71209167HCID 71209167, 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 1-(bromomethyl)-2,3-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 (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) δ ppm 7.49-7.40 (m, 1 H), 7.25-7.17 (m, 1 H), 7.15-7.06 (m, 2 H), 7.05-6.97 (m, 2 H), 6.96-6.90 (m, 1 H), 6.28 (dd, J=3.6, 12.4 Hz, 1 H), 5.69-5.62 (m, 1 H), 5.61-5.51 (m, 2 H), 4.32-4.25 (m, 2 H), 2.95-2.79 (m, 2 H), 2.78-2.72 (m, 3 H), 2.14-2.04 (m, 2 H), 1.01-0.92 (s, 9 H); LC/MS (m/z) ES+=521.39 (M+1).

Workup

  1. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6c316f4a50424a4b84b295a430135396
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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