Triethylamine → N-(2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-2-methoxy-acetamide

HRID 216132Notes

Reaction equation

HRID 216132 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C:11]2[N:16]=[C:15]([O:17][CH3:18])[N:14]=[C:13]([NH:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[CH:12]=2)[CH:7]=[CH:8][C:9]=1[F:10].C(N(CC)CC)C.[CH3:37][O:38][CH2:39][C:40](Cl)=[O:41]>C(Cl)Cl>[F:10][C:9]1[CH:8]=[CH:7][C:6]([C:11]2[CH:12]=[C:13]([NH:19][CH2:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[N:14]=[C:15]([O:17][CH3:18])[N:16]=2)=[CH:5][C:4]=1[CH2:3][NH:2][C:40](=[O:41])[CH2:39][O:38][CH3:37]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 69064976[6-(3-Aminomethyl-4-fluoro-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride

Product 1

HCID 57636096N-(2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-2-methoxy-acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of [6-(3-aminomethyl-4-fluoro-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine [200 mg, 0.52 mmol, see example 27] and triethylamine (264 mg, 2.61 mmol) in DCM (5 mL) is treated with methoxyacetyl chloride (114 mg, 1.1 mmol) at 0° C. After 15 hours at 4° C. in a refrigerator, the mixture is quenched with water (10 mL) filtered through Chem-Elut. The filtrate is concentrated, and subjected to chromatography on silica gel eluting with 10% MeOH in DCM to give N-(2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-2-methoxy-acetamide, which is treated with saturated solution of hydrogen chloride in EtOAc followed by lyophilization to afford N-(2-Fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-2-methoxy-acetamide hydrochloride [190 mg, 74%, Example 28]. LCMS: RT=2.35 minutes, MS: 455 (M+H). IC50=9 nM

Workup

  1. customthe mixture is quenched with water (10 mL)
  2. filtrationfiltered through Chem-Elut
  3. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-a0b39d5522ca46b2a93e37229fad9abb
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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