Hydrochloric Acid → 4-(6-Chloro-pyrimidin-4-ylmethyl)-phenylamine

HRID 1993551Notes

Reaction equation

HRID 1993551 reaction equation
Cl.O1CCOCC1.C(OC(=O)[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]2[CH:27]=[C:26]([Cl:28])[N:25]=[CH:24][N:23]=2)=[CH:17][CH:16]=1)(C)(C)C>C(Cl)Cl>[Cl:28][C:26]1[N:25]=[CH:24][N:23]=[C:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([NH2:14])=[CH:16][CH:17]=2)[CH:27]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 58659459Tert-butyl 4-((6-chloropyrimidin-4-yl)methyl)phenylcarbamate

Product 1

HCID 858915834-(6-Chloro-pyrimidin-4-ylmethyl)-phenylamineYield 148.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 4 N solution of HCl in dioxane (1.2 mL, 4.96 mmol, 30 equiv) is added to a solution of [4-(6-chloro-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (50 mg, 0.156 mmol) in CH2Cl2 (0.67 mL), under an argon atmosphere. The resulting white suspension is stirred at rt for 4 h and concentrated in vacuo to afford 50.9 mg of crude 4-(6-chloro-pyrimidin-4-ylmethyl)-phenylamine as a white solid. DIEA (80 μL, 0.454 mmol, 2 equiv) is added to a suspension of crude 4-(6-chloro-pyrimidin-4-ylmethyl)-phenylamine (50 mg, 0.227 mmol) in THF (0.4 mL), under an argon atmosphere. 4-Ethyl-phenyl-isocyanate (40 μL, 0.250 mmol, 1.1 equiv) is then added. The resulting yellow solution is stirred at rt for 2 h and concentrated in vacuo. The residue is purified by silica gel (20 g) column chromatography (CH2Cl2/MeOH, 98/2). A second purification affords the title compound as a white solid: ES-MS: 367.0 [M+H]+; single peak at tR=8.94 min (System 2); Rf=0.32 (CH2Cl2/MeOH, 95/5).

Workup

  1. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-805d2bdb00004000b139aeba0ead2b99
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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