Tetrafluoro-m-phenylenediamine dihydrochloride → 1-[6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-{4-[2-(pyrrolidin-1-yl)ethyl]piperidin-1-yl}-1,5-naphthyridin-3-yl]ethanone dihydrochloride

HRID 526104Notes

Reaction equation

HRID 526104 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:17][CH2:16]1.[Cl:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([F:44])[C:30]=1[OH:45].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>>[ClH:1].[ClH:28].[Cl:28][C:29]1[CH:34]=[C:33]([C:2]2[N:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]3[N:15]2[CH2:16][CH2:17][CH:18]([CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH2:19][CH2:20]2)[CH:32]=[C:31]([F:44])[C:30]=1[OH:45]

Participants

4

Reactant 3

HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 667160792-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 117774278HCID 117774278, compound

Product 1

HCID 1362667171-[6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-{4-[2-(pyrrolidin-1-yl)ethyl]piperidin-1-yl}-1,5-naphthyridin-3-yl]ethanone dihydrochlorideYield 111.4%

Procedure

Following general procedure II, 1-(6-chloro-4-{4-[2-(pyrrolidin-1-yl)ethyl]piperidin-1-yl}-1,5-naphthyridin-3-yl)ethanone (60 mg, 0.16 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (61 mg, 0.23 mmol) followed by formation of the dihydrochloride salt to afford the desired product (73 mg, 83%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.91 (s, 1H), 8.45 (d, J=9.0 Hz, 1H), 8.35 (d, J=8.9 Hz, 1H), 8.04 (t, J=1.8 Hz, 1H), 7.89 (dd, J=11.7, 2.2 Hz, 1H), 4.66 (br s, 2H), 3.69-3.54 (m, 4H), 3.33-3.23 (m, 2H), 3.13-3.03 (m, 2H), 2.67 (s, 3H), 2.22-1.96 (m, 7H), 1.81-1.68 (m, 4H); ESI MS m/z 497 [M+H]+; HPLC>99% (AUC), tR=9.65 min.

Sources & evidence

ORD record
ord-09459876ed414443a6fed05e1f262fae
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

Loading…