2-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → (S)-(4-(6-(3-aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)(cyclopropyl)methanone

HRID 2271898Notes

Reaction equation

HRID 2271898 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[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(=O)OC(C)(C)C)[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]([F:54])[C:40]=1[OH:55]>>[NH2:30][C@H:26]1[CH2:27][CH2:28][CH2:29][N:24]([C:21]2[N:22]=[CH:23][C:18]([NH:17][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([C:43]5[CH:42]=[C:41]([F:54])[C:40]([OH:55])=[C:39]([Cl:38])[CH:44]=5)[CH:3]=4)[N:8]=[CH:7][C:6]=3[C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[CH:19][CH:20]=2)[CH2:25]1

Participants

3

Reactant 2

HCID 667160792-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 86692881HCID 86692881, compound

Product 1

HCID 66716424(S)-(4-(6-(3-aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)(cyclopropyl)methanoneYield 30%

Procedure

Following general procedure D, (S)-tert-butyl 1-(5-(6-bromo-3-(cyclopropanecarbonyl)quinolin-4-ylamino)pyridin-2-yl)piperidin-3-ylcarbamate (100 mg, 0.17 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (71 mg, 0.26 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (27 mg, 30% over 2 steps) as an orange-yellow solid: 1H NMR (500 MHz, MeOD TFA-d) δ 9.40 (br s, 1H), 8.28-8.15 (m, 2H), 8.06 (br s, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.66 (dd, J=9.1, 2.8 Hz, 1H), 7.16-7.05 (m, 3H), 4.53 (d, J=11.0 Hz, 1H), 4.01 (dd, J=13.4, 4.6 Hz, 1H), 3.41-3.23 (m, 3H), 2.86 (br s, 1H), 2.23-2.15 (m, 1H), 1.99-1.88 (m, 1H), 1.79-1.66 (m, 2H), 1.27-1.16 (m, 4H). ESI MS m/z 532 [C29H27ClFN5O2+H]+; HPLC>99.0% (AUC), tR=10.78 min.

Workup

  1. customto obtain the protected intermediate which

Sources & evidence

ORD record
ord-0f382596abd34a8eb5a6786d81490e10
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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