2-Aminophenol → HCID 58997059, compound

HRID 1592600Notes

Reaction equation

HRID 1592600 reaction equation
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:33](Cl)(Cl)=[O:34].[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[OH:44]>C1(C)C=CC=CC=1>[OH:44][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[NH:37][C:33]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:8][C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:11][CH2:12]1)=[O:34]

Participants

6

Reactant 4

HCID 58012-AminophenolHCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997059HCID 58997059, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of COMPOUND 249 (0.1537 g, 0.50 mmol) in toluene (5 mL) was added DIPEA (0.17 mL, 1.00 mmol), and at 0° C. was added a 20% phosgene solution in toluene (0.27 mL, 0.59 mmol). The reaction was stirred at room temperature for 2 hours, then concentrated. The remaining solid was dissolved in DMF (5 mL), and DIPEA (0.17 mL, 1.00 mmol) and 2-aminophenol (0.2353 g, 2.50 mmol) were added, and stirred at room temperature for 20 hours. The mixture was concentrated, and saturated NaHCO3 (20 mL) was added and extracted with CH2Cl2 (3×40 mL). The combined organic extracts were washed with brine (2×30 mL), dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (50:1:1 then 20:1:1 CH2Cl2-MeOH—NH4OH) followed by radial chromatography (20:1:1 CH2Cl2-MeOH—NH4OH) provided 56.0 mg (24%) of COMPOUND 343 as a brown solid. 1H NMR (CD3OD) δ 1.70-1.78 (m, 2H), 1.91-1.95 (m, 2H), 2.15 (s, 6H), 2.68 (t, 3H, J=12.6 Hz), 3.85 (s, 4H), 4.23 (d, 2H, J=14.1 Hz), 6.68-6.71 (m, 2H), 7.08-7.11 (m, 2H), 7.21-7.25 (m, 2H), 7.55 (d, 2H, J=7.8 Hz), 8.27 (d, 2H, J=4.5 Hz). 13C NMR (DMSO) δ 17.76, 27.09, 44.12, 54.56, 57.81, 115.03, 122.36, 122.84, 128.41, 132.36, 133.23, 138.16, 145.97, 152.75, 155.37, 157.39. ES-MS m/z 446.5 (M+H). Anal. Calcd. for C26H31N5O.0.3(CH2Cl2).0.2H2O: C, 67.06; H, 6.76; N, 14.87. Found: C, 67.17; H, 6.83; N, 14.58.

Workup

  1. concentrationconcentrated
  2. dissolutionThe remaining solid was dissolved in DMF (5 mL)
  3. stirringstirred at room temperature for 20 hours
  4. concentrationThe mixture was concentrated
  5. additionsaturated NaHCO3 (20 mL) was added
  6. extractionextracted with CH2Cl2 (3×40 mL)
  7. washThe combined organic extracts were washed with brine (2×30 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the crude material by column chromatography on silica gel (50:1:1

Sources & evidence

ORD record
ord-5b71c70ff61b46fe94cf77f836c14f38
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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