2,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → (S)-tert-butyl 1-{5-[3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-4-ylamino]pyridin-2-yl}piperidin-3-ylcarbamate

HRID 526188Notes

Reaction equation

HRID 526188 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[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]2)=[N:22][CH:23]=1.[Cl:38][C:39]1[CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:42]=[C:41]([Cl:54])[C:40]=1[OH:55]>>[CH:14]1([C:12]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]4[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:25]4)=[N:22][CH:23]=2)=[N:3][C:2]([C:43]2[CH:44]=[C:39]([Cl:38])[C:40]([OH:55])=[C:41]([Cl:54])[CH:42]=2)=[CH:11][CH:10]=3)=[O:13])[CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 667151272,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 117774124(S)-tert-Butyl 1-{5-[6-chloro-3-(cyclopropanecarbonyl)-1,5-naphthyridin-4-ylamino]-pyridin-2-yl}piperidin-3-ylcarbamate

Product 1

HCID 136927262(S)-tert-butyl 1-{5-[3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-4-ylamino]pyridin-2-yl}piperidin-3-ylcarbamateYield 60%

Procedure

Following general procedure II, (S)-tert-butyl 1-{5-[6-chloro-3-(cyclopropanecarbonyl)-1,5-naphthyridin-4-ylamino]pyridin-2-yl}piperidin-3-ylcarbamate (98 mg, 0.19 mmol) was reacted with 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (87 mg, 0.30 mmol) to afford the desired product (73 mg, 60%) as a red-brown solid: 1H NMR (500 MHz, CDCl3) δ 11.55 (br s, 1H), 9.29 (s, 1H), 8.25 (d, J=8.8 Hz, 1H), 8.03 (d, J=2.7 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.46 (s, 2H), 7.32 (dd, J=9.0, 2.8 Hz, 1H), 6.67 (d, J=9.0 Hz, 1H), 4.78-4.72 (m, 1H), 3.87-3.69 (m, 3H), 3.29-3.07 (m, 2H), 2.79-2.71 (m, 1H), 1.98-1.69 (m, 2H), 1.45 (s, 9H), 1.31-1.22 (m, 2H), 1.16-1.06 (m, 2H); ESI MS m/z 649 [M+H]+

Sources & evidence

ORD record
ord-52001703e11b44f1b4704d0626a69da1
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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