2,6-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → Cyclopropyl[6-(3,5-difluoro-4-hydroxyphenyl)-4-{4-[1-(dimethylamino)ethyl]piperidin-1-yl}quinolin-3-yl]methanone

HRID 2271728Notes

Reaction equation

HRID 2271728 reaction equation
Br[C:2]1[CH: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[N:17]1[CH2:22][CH2:21][CH:20]([CH:23]([N:25]([CH3:27])[CH3:26])[CH3:24])[CH2:19][CH2:18]1.[F: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]>>[CH:14]1([C:12]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[N:17]2[CH2:22][CH2:21][CH:20]([CH:23]([N:25]([CH3:26])[CH3:27])[CH3:24])[CH2:19][CH2:18]2)=[CH:3][C:2]([C:33]2[CH:34]=[C:29]([F:28])[C:30]([OH:45])=[C:31]([F:44])[CH:32]=2)=[CH:11][CH:10]=3)=[O:13])[CH2:16][CH2:15]1

Participants

3

Reactant 2

HCID 576554062,6-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 86692863(6-Bromo-4-{4-[1-(dimethylamino)ethyl]piperidin-1-yl}quinolin-3-yl)(cyclopropyl)methanone

Product 1

HCID 86692922Cyclopropyl[6-(3,5-difluoro-4-hydroxyphenyl)-4-{4-[1-(dimethylamino)ethyl]piperidin-1-yl}quinolin-3-yl]methanoneYield 45%

Procedure

Following general procedure F, (6-bromo-4-{4-[1-(dimethylamino)ethyl]piperidin-1-yl}quinolin-3-yl)(cyclopropyl)methanone (60 mg, 0.139 mmol) was reacted with 2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (39 mg, 0.153 mmol) to afford the desired product (30 mg, 44%) as a light yellow solid: 1H NMR (300 MHz, CD3OD) δ 8.82 (s, 1H), 8.26 (s, 1H), 8.03 (p, J=8.8 Hz, 2H), 7.35 (dd, J=8.0, 1.7 Hz, 2H), 3.56 (t, J=10.3 Hz, 2H), 3.26-3.17 (m, 3H), 2.80 (s, 6H), 2.66-2.53 (m, 1H), 1.96 (d, J=11.2 Hz, 3H), 1.87-1.68 (m, 2H), 1.37-1.22 (m, 8H); ESI MS m/z 480 [C28H31F2N3O2+H]+; HPLC 98.6% (AUC), tR=10.24 min.

Sources & evidence

ORD record
ord-c4c493f6f3944aeead82973bc990da2e
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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