N,N-Dimethyl-3-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)oxy)propan-1-amine → N-[3-({5-[2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]-2-Pyridinyl}oxy)propyl]-N,N-dimethylamine

HRID 450188Notes

Reaction equation

HRID 450188 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[CH3:26][N:27]([CH3:47])[CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1>>[F:24][CH:23]([F:25])[C:15]1[N:14]([C:4]2[N:3]=[C:2]([C:35]3[CH:36]=[CH:37][C:32]([O:31][CH2:30][CH2:29][CH2:28][N:27]([CH3:26])[CH3:47])=[N:33][CH:34]=3)[CH:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:5]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=1

Participants

3

Reactant 2

HCID 17998906N,N-Dimethyl-3-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)oxy)propan-1-amineHCID 442492591-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-1H-benzimidazole

Product 1

HCID 49869213N-[3-({5-[2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]-2-Pyridinyl}oxy)propyl]-N,N-dimethylamineYield 33%

Procedure

Similarly, reaction of 1-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-1H-benzimidazole and N,N-dimethyl-3-{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]oxy}-1-propanamine, as in Example 47, gave N-[3-({5-[2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]-2-Pyridinyl}oxy)propyl]-N,N-dimethylamine in 33% yield: mp (CH2Cl2/hexanes) 140-141° C.; 1H NMR (DMSO-d6) δ 9.07 (d, J=2.2 Hz, 1H), 8.53 (dd, J=8.8, 2.5 Hz, 1H), 8.37 (d, J=8.2 Hz, 1H), 7.87 (d, J=7.9 Hz, 1H), 7.80 (t, JHF=52.8 Hz, 1H), 7.52 (dt, J=7.8, 1.0 Hz, 1H), 7.50 (dd J=8.1, 1.0 Hz, 1H), 7.42 (s, 1H), 7.00 (d, J=8.7 Hz, 1H), 4.39 (t, J=6.6 Hz, 2H), 3.85-3.84 (m, 4H), 3.78-3.76 (m, 4H), 2.39 (t, J=7.1 Hz, 2H), 2.17 (s, 6H), 1.89 (quintet, 2H); Anal. Calcd. for C26H29F2N7O: C, 61.3; H, 5.7; N, 19.2. Found: C, 61.0; H, 5.5; N, 19.1%.

Sources & evidence

ORD record
ord-484e9d5f3be0432f9b5f35cd4de6b095
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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