1-Pyrrolidineethanamine → HCID 11540679, compound

HRID 216129Notes

Reaction equation

HRID 216129 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14]2[N:19]=[C:18]([O:20][CH3:21])[N:17]=[C:16]([C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25]([OH:27])=O)[CH:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.[NH2:53][CH2:54][CH2:55][N:56]1[CH2:60][CH2:59][CH2:58][CH2:57]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14]2[N:19]=[C:18]([O:20][CH3:21])[N:17]=[C:16]([C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25]([NH:53][CH2:54][CH2:55][N:56]3[CH2:60][CH2:59][CH2:58][CH2:57]3)=[O:27])[CH:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 5

HCID 13441-PyrrolidineethanamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57636006HCID 57636006, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 11540679HCID 11540679, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-{6-[2-(3,4-dimethoxy-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid [0.15 mmol, Example 35(k)], hydroxybenzotriazole (41 mg, 0.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (58 mg, 0.3 mmol), N-(2-aminoethyl)pyrrolidine (38 μL, 0.3 mmol) and N,N-diisopropylethylamine (105 μL, 0.6 mmol) in DCM (3 mL) is stirred at ambient temperature under a nitrogen atmosphere for 18 hours. The reaction is poured into water (20 mL) and extracted twice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated by rotary evaporator. The resulting solid is subjected to flash column chromatography on silica gel eluting with 10 to 60% EtOAc in heptane gradient to afford 3-{6-[2-(3,4-dimethoxy-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide [18 mg, 24%, Example 25(b)]. LCMS: RT=2.1 minutes, MS: 506 (M+H). IC50=30 nM

Workup

  1. extractionextracted twice with EtOAc (25 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated by rotary evaporator

Sources & evidence

ORD record
ord-9f9be71339ee43de9caeb6475a1feb2d
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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