Hydrochloric Acid → 6-Chloro-16-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(11,15)]pentacosa-1(23),3(25),4,6,11(24),12,14,19,21-nonaene

HRID 1614951Notes

Reaction equation

HRID 1614951 reaction equation
Br[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[N:16]=[C:15]([NH:17][CH2:18][CH2:19][C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=3)[C:14]([Cl:27])=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1.[OH-].[Na+].Cl>O1CCCC1.O>[Cl:27][C:14]1[CH:13]=[N:12][C:11]2[NH:10][C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([CH:5]=3)[CH2:3][CH2:2][O:26][C:22]3[CH:21]=[C:20]([CH2:19][CH2:18][NH:17][C:15]=1[N:16]=2)[CH:25]=[CH:24][CH:23]=3

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 584678313-{2-[(2-{[3-(2-Bromoethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]ethyl}phenol

Product 1

HCID 468647056-Chloro-16-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(11,15)]pentacosa-1(23),3(25),4,6,11(24),12,14,19,21-nonaeneYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{2-[(2-{[3-(2-bromoethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]ethyl}phenol (50.0 mg, 0.112 mmol) in tetrahydrofuran (1.09 mL) was added a solution of sodium hydroxide in water (0.893 mL, 0.50 M). The resultant solution was stirred at rt for 2 days until the reaction was complete. The reaction was neutralized with HCl (3 M, aqueous solution) to pH 7. The aqueous layer was extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, filtered, and concentrated to give the crude, which was purified by silica gel column chromatography to give the desired product as a white powder (8.5 mg, 21%). LCMS for C20H20ClN4O (M+H)+: m/z=367.0. 1H NMR (400 MHz, CD3OD): δ 7.81 (s, 1H), 7.70 (s, 1H), 7.57 (m, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.08 (m, 2H), 6.69 (s, 1H), 6.67 (m, 2H), 5.73 (dd, J=6.8, 0.8 Hz, 2H), 5.14 (dd, J=7.2, 1.2 Hz, 2H), 3.72 (t, J=7.6 Hz, 2H), 2.86 (t, J=7.6 Hz, 2H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc twice
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude, which
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6ce15d9273a94aa9b53998e72517b1ff
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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