Tetrahydrofuran → HCID 67253094, compound

HRID 1798201Notes

Reaction equation

HRID 1798201 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].[CH3:26][O:27][C:28]1[CH:35]=[C:34](OC)[CH:33]=[CH:32][C:29]=1[CH2:30][NH2:31].C(N(CC)CC)C.C1C[O:48][CH2:47]C1>>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:31][CH2:30][C:29]4[CH:32]=[C:33]([O:48][CH3:47])[CH:34]=[CH:35][C:28]=4[O:27][CH3:26])[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 5972502,4-DimethoxybenzylamineHCID 58292555HCID 58292555, compound

Product 1

HCID 67253094HCID 67253094, compoundYield 51%

Conditions

Temperature
60 °C

Procedure

A solution of [6-(2-chloro-pyrimidin-4-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.50 g, 1.38 mmol) in THF (10 mL) was treated with 2,4-dimethoxybenzylamine (0.41 mL, 2.73 mmol) followed by triethylamine (0.77 mL, 5.52 mmol). The mixture was heated at 60° C. in a sealed tube for 2 days. The solid was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC (CH3CN/0.1% formic acid in water) to give {6-[2-(2,5-dimethoxy-benzylamino)-pyrimidin-4-yloxy]-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl}-acetic acid ethyl ester as a light yellow solid (0.35 g, 51%). 1H NMR (400 MHz, CD3OD) δ 8.04 (d, J=5.71 Hz, 1H), 7.17 (s, 1H), 7.04 (s, 1H), 6.60-6.22 (m, 3H), 6.14 (d, J=5.71 Hz, 1H), 5.69-5.64 (m, 1H), 4.10-4.00 (m, 4H), 3.78 (s, 3H), 3.75 (s, 3H), 3.16 (dd, J=14.91, 2.86 Hz, 1H), 2.43 (dd, J=14.91, 8.73 Hz, 1H), 2.36 (s, 3H), 1.20 (t, J=7.30 Hz, 3H).

Workup

  1. filtrationThe solid was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by preparative HPLC (CH3CN/0.1% formic acid in water)

Sources & evidence

ORD record
ord-c6f1ac0647d145948c5d42b7342230fa
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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