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)propan-1-one

HRID 2271919Notes

Reaction equation

HRID 2271919 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](=[O:15])[CH2:13][CH3:14])=[C:5]2[NH:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[CH2:27][CH2:26][CH:25]([NH:28]C(=O)OC(C)(C)C)[CH2:24]2)=[N:21][CH:22]=1.[Cl:36][C:37]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[C:39]([O:52][CH3:53])[C:38]=1[OH:54]>>[NH2:28][CH:25]1[CH2:26][CH2:27][N:23]([C:20]2[N:21]=[CH:22][C:17]([NH:16][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([C:41]5[CH:40]=[C:39]([O:52][CH3:53])[C:38]([OH:54])=[C:37]([Cl:36])[CH:42]=5)[CH:3]=4)[N:8]=[CH:7][C:6]=3[C:12](=[O:15])[CH2:13][CH3:14])=[CH:18][CH:19]=2)[CH2:24]1

Participants

3

Reactant 2

HCID 177502302-Chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 66716381Tert-butyl 1-(5-(6-bromo-3-propionylquinolin-4-ylamino)pyridin-2-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 667160771-(4-(6-(3-Aminopyrrolidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-4-hydroxy-5-methoxyphenyl)quinolin-3-yl)propan-1-oneYield 27%

Procedure

Following general procedure D, tert-butyl 1-(5-(6-bromo-3-propionylquinolin-4-ylamino) pyridin-2-yl)pyrrolidin-3-ylcarbamate (100 mg, 0.18 mmol) was reacted with 2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (80 mg, 0.28 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (24 mg, 27% over two steps) as a yellow solid: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.28 (s, 1H), 8.29-8.23 (m, 2H), 8.06-7.98 (m, 2H), 7.78 (dd, J=9.1, 2.7 Hz, 1H), 7.02 (d, J=2.2 Hz, 1H), 6.92 (d, J=9.1 Hz, 1H), 6.70 (d, J=2.2 Hz, 1H), 4.14-4.06 (m, 1H), 4.04-3.96 (m, 1H), 3.91 (s, 3H), 3.87-3.77 (m, 1H), 3.75-3.66 (m, 2H), 3.23 (q, J=7.1 Hz, 2H), 2.62-2.51 (m, 1H), 2.32-2.22 (m, 1H), 1.27 (t, J=7.1 Hz, 3H); ESI MS m/z 518 [C28H28ClN5O3+H]+; HPLC 98.5% (AUC), tR=9.79 min.

Workup

  1. customto obtain the protected intermediate which

Sources & evidence

ORD record
ord-6b96d15827f6442ca6ab2ca42b5a7529
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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