Isobutanol → HCID 18438013, compound

HRID 1643211Notes

Reaction equation

HRID 1643211 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:43])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]([CH2:25][C:26]2[C:31]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:30]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:29]=[C:28](Cl)[N:27]=2)[CH2:14][C:15]2[CH:24]=[CH:23][C:18]3[O:19][CH2:20][CH2:21][O:22][C:17]=3[CH:16]=2)=[CH:8][CH:7]=1.[CH2:44]([OH:48])[CH:45]([CH3:47])[CH3:46]>C1COCC1.CC(O)=O.O>[CH2:32]([C:31]1[C:26]([CH2:25][N:13]([CH2:12][C:9]2[CH:10]=[CH:11][C:6]([C:5]([OH:4])=[O:43])=[CH:7][CH:8]=2)[CH2:14][C:15]2[CH:24]=[CH:23][C:18]3[O:19][CH2:20][CH2:21][O:22][C:17]=3[CH:16]=2)=[N:27][C:28]([O:48][CH2:44][CH:45]([CH3:47])[CH3:46])=[N:29][C:30]=1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:33][CH2:34][CH3:35]

Participants

7

Reactant 3

HCID 6560IsobutanolHCID 24758Sodium hydrideHCID 58817909HCID 58817909, compound

Product 1

HCID 18438013HCID 18438013, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersion in mineral oil) (˜40 mg) is added to a solution of 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 (46 mg, 0.0804 mmol) in THF (3 mL) containing isobutyl alcohol (0.5 mL) at room temperature. The mixture is stirred at room temperature for 5 minutes and then at reflux for 2 hours. Next, H2O (0.5 mL) is added and heating is continued for an additional 30 minutes. After cooling to room temperature, the reaction mixture is treated with a few drops of AcOH until pH 4-5. The mixture is then diluted with H2O and extracted twice with CH2Cl2. The combined extracts are dried over Na2SO4 and concentrated. The residue is purified by preparative TLC, eluting with 20:1 CHCl3—MeOH. The band containing the product affords 28.4 mg 4-{[(5-butyl-2-isobutoxy-6-phenyl-pyrimidin-4-ylmethyl)-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-methyl}-benzoic acid as a colorless gum. 1H NMR (CDCl3, 300 MHz) δ 8.02 (br, 2H), 7.39 (br, 7H), 6.87 (br s, 1H), 6.78 (br s, 2H), 4.21 (br s, 4H), 4.12 (br d, J=6.3 Hz, 2H), 3.70 (br, 4H), 3.54 (br s, 2H), 2.54 (br m, 2H), 2.13 (br, 1H), 1.02 (d, J=6.3 Hz, 6H), 0.94 (br 4H), 0.60 (br, 3H) ppm. MS: m/z 596 [M+1].

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureheating
  3. waitis continued for an additional 30 minutes
  4. temperatureAfter cooling to room temperature
  5. extractionextracted twice with CH2Cl2
  6. dry with materialThe combined extracts are dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue is purified by preparative TLC
  9. washeluting with 20:1 CHCl3—MeOH
  10. additionThe band containing the product

Sources & evidence

ORD record
ord-bb46c2417b0d4b1cb3a99b1e1fb2b4e5
Source dataset
uspto-grants-2012_02
Patent number
US08119665B2

Reaction notes

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