5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine → HCID 67283437, compound

HRID 1910698Notes

Reaction equation

Cl[C:2]1[C:3]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:4]=2[N:5]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:6](=[O:20])[CH:7]([CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)[N:8]=1.[NH2:35][C:36]1[CH:41]=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][N:37]=1>>[NH2:35][C:36]1[N:37]=[CH:38][C:39]([C:2]2[C:3]3[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:4]=3[N:5]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:6](=[O:20])[CH:7]([CH2:9][C:10]3[CH:11]=[CH:12][C:17]4[C:18](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:19]=3)[N:8]=2)=[CH:40][CH:41]=1

Participants

Reactant 2

HCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

HCID 67282421HCID 67282421, compound

Product 1

HCID 67283437HCID 67283437, compound

Procedure

5,7-Dichloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.10 g, 0.20 mmol) and 2-aminopyridine-5-boronic acid pinacol ester were reacted according to the corresponding procedure described in Example 12 to yield intermediate 5-(6-aminopyridin-3-yl)-7-chloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one. (77 mg, 69%). 5-(6-Aminopyridin-3-yl)-7-chloro-1-(4-methoxybenzyl)-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (77 mg, 0.14 mmol) was dissolved in anhydrous anisole (2 mL) under a nitrogen atmosphere, and aluminum bromide (1M in dichloromethane, 0.70 mL, 0.70 mmol) was added. The mixture was heated to 80° C. for 1 hour then cooled to ambient temperature and an additional amount of aluminum bromide (1M in dichloromethane, 0.70 mL, 0.70 mmol) was added. The solution was heated to 80° C. for 1 hour, cooled, poured into ice, diluted with ethyl acetate and saturated sodium bicarbonate. The layers were separated and the organic layer dried with sodium sulfate, decanted and concentrated in the presence of silica gel. Column chromatography eluting with a gradient of 70-100% ethyl acetate in hexanes provided 5-(6-aminopyridin-3-yl)-7-chloro-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (25 mg, 42% yield). 1H NMR (300 MHz, d6-DMSO) δ 3.47 (m, 2H) 3.71 (m, 1H), 6.40-6.46 (m, 2H), 7.20-7.26 (m, 2H), 7.42-7.62 (m, 5H), 7.78-7.87 (m, 4H), 10.64 (s, 1H); ESI m/z measured 427.1324 [M+H]+. calculated 427.1326.

Sources & evidence

ORD record: ord-485bdad6eab04169aa6a26216a94a22f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604023B2

Reaction notes

Loading…