Hydrochloric Acid → 4-(6-Chloro-pyrimidin-4-ylmethyl)-phenylamine
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]=1Participants
Procedure
A 4 N solution of HCl in dioxane (11.7 mL, 46.9 mmol, 30 equiv) is added to a solution of [4-(6-chloro-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (Example 117) (0.50 g, 1.56 mmol) in CH2Cl2 (6.7 mL), under an argon atmosphere. The resulting white suspension is stirred at rt for 6.5 h. Additional 4 N HCl solution (1.1 mL, 4.6 mmol, 3.0 equiv) is added. The reaction mixture is allowed to stir for 0.5 h and concentrated in vacuo to afford 0.467 g of crude 4-(6-chloro-pyrimidin-4-ylmethyl)-phenylamine as a white solid. An 8 M solution of methylamine in EtOH (5.1 mL, 40.0 mmol, 30 equiv) Is added to a solution of crude 4-(6-chloro-pyrimidin-4-ylmethyl)phenylamine (0.300 g, 1.37 mmol) in EtOH (2.7 mL), under an argon atmosphere. The mixture Is heated to 50° C. (oil bath temperature) for 5 h, allowed to cool to rt and concentrated in vacuo. The residue is purified by silica gel (48 g) column chromatography (CH2Cl2/MeOH, 85/15) to afford the title compound as a light yellow oil: ES-MS: 215.0 [M+H]+; single peak at tR=3.03 min (System 2); Rf=0.49 (CH2Cl2/MeOH, 85/15).
Workup
- stirringto stir for 0.5 h
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-4a4ff28bf41149038ceb23fffb2ccea9
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07652022B2
Reaction notes
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