Phenol → 6-(4-Chlorophenyl)-3-({6-[(1-methylpiperidin-4-yl)oxy]pyridin-2-yl}methyl)thieno[3,2-d]pyrimidin-4(3H)-one

HRID 2239338Notes

Reaction equation

HRID 2239338 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]([O:15]C)=O)=[C:10](/[N:17]=[CH:18]/[N:19]([CH3:21])C)[CH:9]=2)=[CH:4][CH:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[N:35]=[C:34](CN)[CH:33]=[CH:32][CH:31]=2)[CH2:25][CH2:24]1.C1(O)C=CC=CC=1>C(OCC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]3[C:13](=[O:15])[N:19]([CH2:21][C:34]4[CH:33]=[CH:32][CH:31]=[C:30]([O:29][CH:26]5[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]5)[N:35]=4)[CH:18]=[N:17][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 622878781-{6-[(1-Methylpiperidin-4-yl)oxy]pyridin-2-yl}methanamineHCID 178499302HCID 178499302, compound

Product 1

HCID 247858026-(4-Chlorophenyl)-3-({6-[(1-methylpiperidin-4-yl)oxy]pyridin-2-yl}methyl)thieno[3,2-d]pyrimidin-4(3H)-oneYield 33.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
130 °C

Procedure

Methyl 5-(4-chlorophenyl)-3-{[(1E)-(dimethylamino)methylene]amino}thiophene-2-carboxylate (1.39 g, 4.29 mmol) and 1-{6-[(1-methylpiperidin-4-yl)oxy]pyridin-2-yl}methanamine (0.950 g, 4.29 mmol, from step b above) were mixed with 4 g of phenol and heated to 130° C. on an oil bath for 1 h. When the mixture had cooled down it was diluted with 150 mL of diethyl ether. The mixture became opaque and left overnight. Very little had precipitated but when evaporation of ether was commenced much precipitate was formed and filtered off. The material was recrystallized from ethanol, filtered, washed with ethanol and dried to give 0.675 g (32%) of the desired compound. Mp 202-203° C. 1H NMR (600 MHz, CD3OD) δ 8.43 (s, 1H), 7.75 (m, 2H), 7.65 (s, 1H), 7.60 (t, 1H), 7.45 (m, 2H), 6.95 (d, 1H), 6.55 (d, 1H), 5.30 (s, 2H), 4.55 (br, 1H), 2.52 (m, 2H), 2.05 (s, 3H), 1.84 (m, 2H), 1.70 (m, 2H), 1.51 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 162.7, 157.9, 157.0, 151.9, 151.6, 149.1, 140.1, 135.9, 131.7, 129.7, 127.9, 123.0, 121.1, 115.7, 111.2, 51.4, 50.3, 44.6, 28.7, 22.1. MS (ESI+) 467/469 (M+1H+).

Workup

  1. temperatureWhen the mixture had cooled down it
  2. customVery little had precipitated
  3. customwhen evaporation of ether
  4. customwas formed
  5. filtrationfiltered off
  6. customThe material was recrystallized from ethanol
  7. filtrationfiltered
  8. washwashed with ethanol
  9. customdried

Sources & evidence

ORD record
ord-572cc26249224b37a7bf3c2258079c8c
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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