HCID 19780039, compound → HCID 58174201, compound

HRID 339806Notes

Reaction equation

HRID 339806 reaction equation
[F:1][C:2]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][NH:20][C:21]3[C:30]4[C:25](=[N:26][CH:27]=[CH:28][N:29]=4)[N:24]=[CH:23][N:22]=3)=[CH:14][C:13]=2[O:31]C)[CH:6]=1)([F:4])[CH3:3].B(Br)(Br)Br.CCCCCC>C(Cl)Cl>[F:4][C:2]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][NH:20][C:21]3[C:30]4[C:25](=[N:26][CH:27]=[CH:28][N:29]=4)[N:24]=[CH:23][N:22]=3)=[CH:14][C:13]=2[OH:31])[CH:6]=1)([F:1])[CH3:3]

Participants

4

Reactant 2

HCID 19780039HCID 19780039, compoundHCID 58174116HCID 58174116, compound

Product 1

HCID 58174201HCID 58174201, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-{4-[4-(1,1-difluoroethyl)-pyridin-2-yloxy]-3-methoxyphenyl}-ethyl)-pteridin-4-yl-amine (1.37 g, 3.13 mmol) in CH2Cl2 (15 mL) cooled to 0° C., was added 1M BBr3/hexane (9.4 mL, 9.4 mmol). The solution was allowed to warm to room temperature and stirred overnight. The reaction was quenched with methanol and concentrated in vacuo. The residue was dissolved in small amount of methanol and poured into aqueous NaHCO3. The hydroxyaryl product precipitated and was collected by suction filtration and washed with H2O. The filter cake was air dried on the filter to yield 2-[4-(1,1-difluoroethyl)-pyridin-2-yloxy]-5-[2-(pteridin-4-ylamino)-ethyl]-phenol (0.76 g), as a light brown solid: 1H NMR (300 MHz, d6-DMSO) δ 9.53 (br s, 1H), 9.45 (s, 1H), 9.12 (s, 1H), 8.91 (d, J=1.5 Hz, 1H), 8.78 (br, 1H), 8.20 (d, J=5.3 Hz, 1H), 7.22 (d, J=5.3 Hz, 1H), 7.08 (s, 1H), 6.98 (d, J=8.1 Hz, 1H), 6.85 (d, J=1.8 Hz, 1H), 6.72 (dd, J=8.1, 1.8 Hz, 1H), 3.84 (dd, J=14.7, 7.4 Hz, 2H), 2.93 (t, J=7.4 Hz, 2H), 1.98 (t, J=19.2 Hz, 3H); ESIMS m/z 425 ([M+H]+).

Workup

  1. customThe reaction was quenched with methanol
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in small amount of methanol
  4. additionpoured into aqueous NaHCO3
  5. customThe hydroxyaryl product precipitated
  6. filtrationwas collected by suction filtration
  7. washwashed with H2O
  8. customdried on the
  9. filtrationfilter

Sources & evidence

ORD record
ord-f5efc9b26d8947f58f97539d7d38efd7
Source dataset
uspto-grants-2014_11
Patent number
US08895568B2

Reaction notes

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