HCID 66715668, compound → HCID 66716695, compound

HRID 2271910Notes

Reaction equation

HRID 2271910 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]([O:24][CH2:25][CH2:26][NH:27]C(=O)OC(C)(C)C)=[N:22][CH:23]=1.[Cl:35][C:36]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[C:38]([F:51])[C:37]=1[OH:52]>>[NH2:27][CH2:26][CH2:25][O:24][C:21]1[N:22]=[CH:23][C:18]([NH:17][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:40]4[CH:39]=[C:38]([F:51])[C:37]([OH:52])=[C:36]([Cl:35])[CH:41]=4)[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])=[CH:19][CH:20]=1

Participants

3

Reactant 2

HCID 66715668HCID 66715668, compoundHCID 667160792-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol

Product 1

HCID 66716695HCID 66716695, compoundYield 26%

Procedure

Following general procedure D, tert-butyl 2-(5-(6-bromo-3-(cyclopropanecarbonyl)quinolin-4-ylamino)pyridin-2-yloxy)ethylcarbamate (100 mg, 0.19 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (76 mg, 0.28 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (24 mg, 26% over two steps) as a yellow solid: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.40 (s, 1H), 8.34-8.24 (m, 2H), 8.13-8.03 (m, 2H), 7.82 (dd, J=8.8, 2.8 Hz, 1H), 7.24-7.10 (m, 3H), 4.65 (t, J 5.1=Hz, 2H), 3.43 (t, J=5.1 Hz, 2H), 2.87-2.81 (m, 1H), 1.23-1.15 (m, 4H); ESI MS m/z 493 [C26H22ClFN4O3+H]+; HPLC>99% (AUC), tR=11.00 min.

Workup

  1. customto obtain the protected intermediate which

Sources & evidence

ORD record
ord-0beb5c614b6d4cac898159a4fef8ddd3
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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