Hydrochloric Acid → 6-Chloro-16-oxa-2,4,8,26-tetraazatetracyclo[18.3.1.1(3,7).1(11,15)]hexacosa-1(24),3(26),4,6,11(25),12,14,20,22-nonaene

HRID 1614963Notes

Reaction equation

HRID 1614963 reaction equation
Br[CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH2:19][CH2:20][C:21]3[CH:22]=[C:23]([OH:27])[CH:24]=[CH:25][CH:26]=3)[C:15]([Cl:28])=[CH:14][N:13]=2)[CH:8]=[CH:9][CH:10]=1.[OH-].[Na+].Cl>O1CCCC1.O>[Cl:28][C:15]1[CH:14]=[N:13][C:12]2[NH:11][C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([CH:6]=3)[CH2:4][CH2:3][CH2:2][O:27][C:23]3[CH:22]=[C:21]([CH2:20][CH2:19][NH:18][C:16]=1[N:17]=2)[CH:26]=[CH:25][CH:24]=3

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 584678483-{2-[(2-{[3-(3-Bromopropyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]ethyl}phenol

Product 1

HCID 468647456-Chloro-16-oxa-2,4,8,26-tetraazatetracyclo[18.3.1.1(3,7).1(11,15)]hexacosa-1(24),3(26),4,6,11(25),12,14,20,22-nonaeneYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{2-[(2-{[3-(3-bromopropyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]ethyl}phenol (50.0 mg, 0.108 mmol) in tetrahydrofuran (1.0 mL) was added a solution of sodium hydroxide in water (1.0 mL, 1.0 M). The resultant solution was stirred at rt for 60 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 a residue, which was purified by silica gel column chromatography to give the desired product as a white powder (4.0 mg, 10%). LCMS for C21H22ClN4O (M+H)+: m/z=381.0. 1H NMR (400 MHz, CD3OD): δ 7.95 (s, 1H), 7.90 (s, 1H), 7.30 (m, 3H), 7.12 (t, J=7.4 Hz, 1H), 6.94 (m, 1H), 6.65 (m, 2H), 3.70 (t, J=7.6 Hz, 2H), 3.48 (t, J=6.8 Hz, 2H), 2.80 (m, 2H), 2.72 (m, 2H), 2.10 (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 a residue, which
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-718ec02163de452a94eebc2970e36c8e
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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