Water → 4-{6-[2-Fluoro-4-(2-morpholin-4-yl-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid isopropyl Ester

HRID 2377939Notes

Reaction equation

HRID 2377939 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[C:27]([CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH:26]=[CH:25][C:24]=1[OH:37].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:37][C:24]3[CH:25]=[CH:26][C:27]([CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[CH:28][C:23]=3[F:22])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 67203226HCID 67203226, compound

Product 1

HCID 598567104-{6-[2-Fluoro-4-(2-morpholin-4-yl-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid isopropyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (270 mg, 0.84 mmol) and 2-fluoro-4-(2-morpholin-4-yl-ethyl)-phenol (225 mg, 0.84 mmol) in DMF (5 mL), was K2CO3 (137 mg, 0.84 mmol) added. The reaction mixture was irradiated under microwave for 1 hour at 150° C. The reaction was cooled to room temperature and poured into H2O (50 mL) and extracted with ethyl acetate (50 mL). The ethyl acetate was dried over MgSO4, and concentrated under vacuum and purified over SiO2 to afford Compound C146 (380 mg, 90%) as a white solid. 1H NMR (400 Mz, DMSO-d6) δ 8.06 (s, 1H), 7.09˜7.02 (m, 1H), 6.93˜6.91 (m, 2H), 5.12 (m, 1H), 4.61 (m, 1H), 3.46˜3.37 (m, 6H), 3.18˜3.13 (m, 2H), 2.61˜2.57 (m, 2H), 2.38˜2.26 (m, 2H), 2.25 (b, 2H), 1.96 (s, 3H), 1.79˜1.74 (m, 2H), 1.49˜1.45 (m, 2H), 1.03 (d, 6H). LCMS 503.5 [M+1].

Workup

  1. additionadded
  2. customThe reaction mixture was irradiated under microwave for 1 hour at 150° C
  3. extractionextracted with ethyl acetate (50 mL)
  4. dry with materialThe ethyl acetate was dried over MgSO4
  5. concentrationconcentrated under vacuum
  6. custompurified over SiO2
  7. customto afford Compound C146 (380 mg, 90%) as a white solid

Sources & evidence

ORD record
ord-81ac486213e04318b0ea91b4414e9c6c
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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