Sodium Hydroxide → 11-Bromo-6-chloro-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaene

HRID 1614971Notes

Reaction equation

HRID 1614971 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH2:9][NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][CH2:26][CH2:27]Br)[CH:20]=2)[N:12]=1.[OH-].[Na+]>O1CCCC1.O.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Br:1][C:2]1[C:3]2[CH2:9][NH:10][C:11]3[N:12]=[C:13]([NH:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([CH:20]=4)[CH2:25][CH2:26][CH2:27][O:8][C:5]([CH:4]=2)=[CH:6][CH:7]=1)[N:14]=[CH:15][C:16]=3[Cl:17]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 584679264-Bromo-3-{[(2-{[3-(3-bromopropyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]methyl}phenol

Product 1

HCID 4686474711-Bromo-6-chloro-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaeneYield 35.4%

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 4-bromo-3-{[(2-{[3-(3-bromopropyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]methyl}phenol (1.00 g, 1.90 mmol) in tetrahydrofuran (9.0 mL) was added a solution of sodium hydroxide in water (18 mL, 4.0 M). The resultant solution was then treated with benzyltriethylammonium chloride (30.0 mg, 0.13 mmol) and heated at 35° C. for 40 hours. The reaction mixture could not be purified by silica gel column chromatography or prep-HPLC. However, after cooling, THF and alkaline NaOH layers could be separated. THF layer was washed with brine and concentrated to give a light yellow solid residue, which was triturated with MeOH/EtOAc (90:10). After vacuum filtration, the cake was washed with MeOH to provide the desired pure product (300 mg, 35%) as an off-white powder. LCMS for C20H18BrClN4O (M+H)+: m/z=444.9, 446.9. 1H NMR (400 MHz, DMSO-d6): δ 8.76 (s, 1H), 7.86 (s, 1H), 7.50 (s, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.27 (m, 1H), 7.16 (m, 1H), 7.04 (m, 2H), 6.68 (m, 1H), 6.20 (m, 1H), 4.23 (m, 2H), 4.02 (t, 2H), 3.15 (m, 1H), 2.65 (m, 2H), 1.96 (m, 2H).

Workup

  1. customThe reaction mixture could not be purified by silica gel column chromatography
  2. temperatureHowever, after cooling
  3. customTHF and alkaline NaOH layers could be separated
  4. washTHF layer was washed with brine
  5. concentrationconcentrated
  6. customto give a light yellow solid residue, which
  7. customwas triturated with MeOH/EtOAc (90:10)
  8. filtrationAfter vacuum filtration
  9. washthe cake was washed with MeOH

Sources & evidence

ORD record
ord-c27a294af5b54e56b22dbc055e0c7d9e
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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