Potassium Carbonate → HCID 58817909, compound

HRID 1643210Notes

Reaction equation

HRID 1643210 reaction equation
Br[CH2:2][C:3]1[C:8]([CH2:9][CH2:10][CH2:11][CH3:12])=[C:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:6]=[C:5]([Cl:19])[N:4]=1.[CH3:20][O:21][C:22](=[O:42])[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH:30][CH2:31][C:32]2[CH:41]=[CH:40][C:35]3[O:36][CH2:37][CH2:38][O:39][C:34]=3[CH:33]=2)=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:20][O:21][C:22](=[O:42])[C:23]1[CH:24]=[CH:25][C:26]([CH2:29][N:30]([CH2:2][C:3]2[C:8]([CH2:9][CH2:10][CH2:11][CH3:12])=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:6]=[C:5]([Cl:19])[N:4]=2)[CH2:31][C:32]2[CH:41]=[CH:40][C:35]3[O:36][CH2:37][CH2:38][O:39][C:34]=3[CH:33]=2)=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18438039HCID 18438039, compoundHCID 66757422HCID 66757422, compound

Product 1

HCID 58817909HCID 58817909, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of impure 4-bromomethyl-5-butyl-2-chloro-6-phenyl-pyrimidine (288 mg) and 4-{[(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-methyl}-benzoic acid methyl ester (190 mg, 0.606 mmol) in CH3CN containing K2CO3 (300 mg) is stirred at room temperature. The reaction is monitored by TLC until complete consumption of 4-bromomethyl-5-butyl-2-chloro-6-phenyl-pyrimidine (24 hours). The mixture is then diluted with CH2Cl2 and filtered. The filtrate is concentrated, and the resulting residue is purified by flash chromatography on silica gel. Elution with 5:1 hexanes-EtOAc followed by 4:1 hexanes-EtOAc affords 215 mg of pure 4-{[(5-butyl-2-chloro-6-phenyl pyrimidin-4-ylmethyl)-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-methyl}-benzoic acid methyl ester 1H NMR (CDCl3, 300 MHz) δ 7.97 (d, J=8.1 Hz, 2H), 7.44-7.33 (m, 7H), 6.84 (s, 1H), 6.79 (s, 2H), 4.22 (s, 4H), 3.90 (s, 3H), 3.74 (s, 2H), 3.72 (s, 2H), 3.55 (s, 2H), 2.64-2.56 (m, 2H), 1.01 (m, 2H), 0.90 (sext, J=7.2 Hz, 2H), 0.61 (t, J=7.2 Hz, 3H) ppm. MS: m/z 572 [M+1].

Workup

  1. customThe reaction is monitored by TLC until complete consumption of 4-bromomethyl-5-butyl-2-chloro-6-phenyl-pyrimidine (24 hours)
  2. additionThe mixture is then diluted with CH2Cl2
  3. filtrationfiltered
  4. concentrationThe filtrate is concentrated
  5. customthe resulting residue is purified by flash chromatography on silica gel
  6. washElution with 5:1 hexanes-EtOAc

Sources & evidence

ORD record
ord-fdb273956992453bb5fda96fcfed459d
Source dataset
uspto-grants-2012_02
Patent number
US08119665B2

Reaction notes

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