2-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → (6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)(cyclobutyl)methanone

HRID 526232Notes

Reaction equation

HRID 526232 reaction equation
Cl[C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:17][CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:18][CH:19]1[CH2:24][CH2:23][CH:22]([CH2:25][N:26]([CH3:28])[CH3:27])[CH2:21][CH2:20]1.[Cl:29][C:30]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46]>>[Cl:29][C:30]1[CH:35]=[C:34]([C:2]2[N:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:15][CH2:16][CH2:17]2)=[O:13])=[C:5]3[NH:18][CH:19]2[CH2:20][CH2:21][CH:22]([CH2:25][N:26]([CH3:27])[CH3:28])[CH2:23][CH2:24]2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46]

Participants

3

Reactant 2

HCID 667160792-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 117774246(6-Chloro-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)(cyclobutyl)methanone

Product 1

HCID 136266755(6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)(cyclobutyl)methanoneYield 88.1%

Procedure

Following general procedure II, (6-chloro-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)(cyclobutyl)methanone (65 mg, 0.16 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (65 mg, 0.24 mmol) to afford the desired product (72 mg, 77%) as light yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.93 (s, 1H), 8.44 (d, J=9.0 Hz, 1H), 8.33 (d, J=9.0 Hz, 1H), 8.02 (s, 1H), 7.88 (dd, J=11.5, 2.0 Hz, 1H), 5.74-5.64 (m, 1H), 4.29-4.19 (m, 1H), 3.12-3.07 (m, 2H), 2.95 (s, 6H), 2.52-2.41 (m, 4H), 2.39-2.34 (m, 2H), 2.24-2.12 (m, 1H), 2.09-1.98 (m, 2H), 1.98-1.89 (m, 1H), 1.78-1.66 (m, 2H), 1.49-1.35 (m, 2H); ESI MS m/z 511 [M+H]+; HPLC>99% (AUC), tR=10.52 min.

Sources & evidence

ORD record
ord-5d0b6d5001784aa0afd489b6995e453c
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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