Hydrochloric Acid → 20-Chloro-9-oxa-2,18,22,23-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 1614955Notes

Reaction equation

HRID 1614955 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2[N:15]=[C:14]([NH:16][CH2:17][CH2:18][CH2:19][C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=3)[C:13]([Cl:27])=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].Cl>O1CCCC1.O>[Cl:27][C:13]1[CH:12]=[N:11][C:10]2=[N:15][C:14]=1[NH:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[C:22]([O:26][CH2:2][C:3]3[CH:4]=[C:5]([NH:9]2)[CH:6]=[CH:7][CH:8]=3)[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58467846HCID 58467846, compound

Product 1

HCID 4686474420-Chloro-9-oxa-2,18,22,23-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaeneYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{3-[(2-{[3-(bromomethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]propyl}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 16 hours until the reaction was complete. The reaction mixture 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 product, which was purified by silica gel column chromatography to give the desired product as a white powder (8 mg, 20%). LCMS for C20H20ClN4O (M+H)+: m/z=367.0. 1H NMR (400 MHz, CD3OD): δ 7.94 (s, 1H), 7.75 (s, 1H), 7.26 (m, 1H), 7.17 (m, 2H), 7.03 (t, J=7.6 Hz, 1H), 6.88 (m, 1H), 6.70 (m, 1H), 6.60 (m, 1H), 5.17 (s, 2H), 3.48 (t, J=7.6 Hz, 2H), 2.74 (t, J=6.8 Hz, 2H), 1.91 (m, 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 product, which
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5f93505017d746ffac7bd4604e649f2a
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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