2-Chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → 1-(4-(6-(3-Aminopyrrolidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-4-hydroxy-5-methoxyphenyl)quinolin-3-yl)ethanone

HRID 2271920Notes

Reaction equation

HRID 2271920 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]3[CH2:25][CH2:24][CH:23]([NH:26]C(=O)OC(C)(C)C)[CH2:22]3)=[N:19][CH:20]=1)=[CH:11][C:10](Br)=[CH:9][CH:8]=2)(=[O:3])[CH3:2].[Cl:35][C:36]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[C:38]([O:51][CH3:52])[C:37]=1[OH:53]>>[NH2:26][CH:23]1[CH2:24][CH2:25][N:21]([C:18]2[N:19]=[CH:20][C:15]([NH:14][C:13]3[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([C:40]5[CH:39]=[C:38]([O:51][CH3:52])[C:37]([OH:53])=[C:36]([Cl:35])[CH:41]=5)[CH:11]=4)[N:6]=[CH:5][C:4]=3[C:1](=[O:3])[CH3:2])=[CH:16][CH:17]=2)[CH2:22]1

Participants

3

Reactant 2

HCID 177502302-Chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 66716524Tert-butyl 1-(5-(3-acetyl-6-bromoquinolin-4-ylamino)pyridin-2-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 667160961-(4-(6-(3-Aminopyrrolidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-4-hydroxy-5-methoxyphenyl)quinolin-3-yl)ethanoneYield 15%

Procedure

Following general procedure D, tert-butyl 1-(5-(3-acetyl-6-bromoquinolin-4-ylamino) pyridin-2-yl)pyrrolidin-3-ylcarbamate (80 mg, 0.15 mmol) was reacted with 2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (65 mg, 0.23 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (11 mg, 15% over two steps) as a yellow-brown: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.28 (s, 1H), 8.31-8.25 (m, 2H), 8.06-7.99 (m, 2H), 7.83 (dd, J=9.2, 2.7 Hz, 1H), 7.04 (d, J=2.2 Hz, 1H), 7.98 (d, J=9.2 Hz, 1H), 6.71 (d, J=2.2 Hz, 1H), 4.16-4.07 (m, 1H), 4.07-3.96 (m, 2H), 3.91 (s, 3H), 3.88-3.79 (m, 1H), 3.79-3.69 (m, 211), 2.80 (s, 3H), 2.63-2.53 (m, 1H), 2.34-2.23 (m, 1H); ESI MS m/z 504 [C27H26ClN5O3+H]+; HPLC 95.4% (AUC), tR=9.37 min.

Workup

  1. customto obtain the protected intermediate which

Sources & evidence

ORD record
ord-aaa8c1ca02b54a349a3345e9488ed004
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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