Lithium Hydroxide → 3-(4-((2-(3-Chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)phenyl)propan-1-ol

HRID 1508843Notes

Reaction equation

HRID 1508843 reaction equation
Cl[C:2]1[C:3]2[CH2:17][CH2:16][CH2:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:7]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH2:27][OH:28])=[CH:21][CH:20]=1.[OH-].[Li+]>C(O)(=O)C.C(=O)(O)[O-].[Na+].O>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:7]=[C:2]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([CH2:25][CH2:26][CH2:27][OH:28])=[CH:23][CH:24]=3)[C:3]3[CH2:17][CH2:16][CH2:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 2204244-AminobenzenepropanolHCID 218826774-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 903385403-(4-((2-(3-Chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)phenyl)propan-1-olYield 40.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

4-Chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (0.090 g, 0.40 mmol) and 3-(4-aminophenyl)propan-1-ol (0.060 g, 0.40 mmol) were suspended in acetic acid (2 mL). The mixture was heated to 120° C. for 1 h. After this time, the reaction was cooled, diluted with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The mixture was concentrated, redissolved in methanol (5 mL), and lithium hydroxide (4 equiv) was added. The mixture stirred for 1 h, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, dichloromethane/ethyl acetate) to afford the title compound (0.061 g, 40%) as a white solid. MW=379.88. 1H NMR (DMSO-d6, 500 MHz) δ 8.83 (s, 1H), 8.28-8.21 (m, 2H), 7.69 (d, J=8.5 Hz, 2H), 7.54-7.49 (m, 2H), 7.20 (d, J=8.5 Hz, 2H), 3.44 (t, J=6.5 Hz, 1H), 2.92-2.85 (m, 4H), 2.61 (t, J=7.5 Hz, 2H), 2.10 (quin, J=7.5 Hz, 2H), 1.76-1.74 (m, 2H); APCI MS m/z 380 [M+H]+.

Workup

  1. temperatureAfter this time, the reaction was cooled
  2. extractionextracted with ethyl acetate
  3. concentrationThe mixture was concentrated
  4. dissolutionredissolved in methanol (5 mL)
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by column chromatography (silica, dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-05acdf119db74a6b916c6c8b14324aec
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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