2-Chloro-6-fluoro-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-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)ethanone

HRID 2271921Notes

Reaction equation

HRID 2271921 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]([F:51])[C:37]=1[OH:52]>>[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]([F:51])[C:37]([OH:52])=[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 667160792-Chloro-6-fluoro-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 866929831-(4-(6-(3-Aminopyrrolidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)ethanoneYield 16%

Procedure

Following general procedure D, tert-butyl 1-(5-(3-acetyl-6-bromoquinolin-4-ylamino) pyridin-2-yl)pyrrolidin-3-ylcarbamate (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 (13 mg, 16% over two steps) as a yellow solid: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.29 (s, 1H), 8.29-8.20 (m, 2H), 8.05-7.99 (m, 2H), 7.84 (dd, J=9.2, 2.6 Hz, 1H), 7.15 (d, J=11.6 Hz, 1H), 7.07 (s, 1H), 7.00 (d, J=9.2 Hz, 1H), 4.17-4.09 (m, 1H), 4.07-4.00 (m, 1H), 3.90-3.81 (m, 1H), 3.80-3.71 (m, 2H), 2.79 (s, 3H), 2.65-2.52 (m, 1H), 2.36-2.25 (m, 1H); ESI MS m/z 492 [C26H23ClFN5O2+H]+; HPLC 97.6% (AUC), tR=9.73 min.

Workup

  1. customto obtain the protected intermediate which

Sources & evidence

ORD record
ord-7ed2be4007e64e37953dc6e877cb2f4b
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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