Hydrochloric Acid → Methyl [4-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](3-piperidin-1-ylpropyl)amino]methyl}phenyl]acetate hydrochloride

HRID 339937Notes

Reaction equation

HRID 339937 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:41])[N:6]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]([O:39][CH3:40])=[O:38])=[CH:32][CH:31]=1)[CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.[ClH:42].CC(OC)(C)C>CO>[ClH:42].[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:41])[N:6]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:29][C:30]1[CH:31]=[CH:32][C:33]([CH2:36][C:37]([O:39][CH3:40])=[O:38])=[CH:34][CH:35]=1)[CH2:20][CH2:21][CH2:22][N:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 15413tert-Butyl methyl ether2×HCID 67989365Methyl (4-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](3-piperidin-1-ylpropyl)amino]methyl}phenyl)acetate

Product 1

HCID 86705742Methyl [4-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](3-piperidin-1-ylpropyl)amino]methyl}phenyl]acetate hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
8 °C

Procedure

A mixture of methyl [4-{[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](3-piperidin-1-ylpropyl)amino]methyl}phenyl]acetate (6.0 g, 10.8 mmol) in MeOH (30 g) was stirred at 8° C. for 10 min. To the suspension, 35% aqueous HCl (1.1 g, 10.67 mmol) in MeOH (6 g mL) was added dropwise and warmed to 23° C. To the mixture was added more MeOH (3 g). MTBE (78 g) was added to the mixture, which was then stirred at 20° C. for 30 min. After seeding and stirring for 30 min, MTBE (42 g) was added, the suspension cooled to 3° C. and stirred for 1 hr. Then the suspension was filtered and collected solid washed with MTBE (15 g) and dried to give the title compound. M.P. 137-139° C. Yield 5.7 g, 90%; 1H NMR (DMSO-d6) δ 10.08 (br, 1H), 7.24 (d, 2H), 7.17 (d, 2H), 6.53 (br, 2H), 4.11 (t, 2H), 3.68 (t, 4H), 3.65 (s, 3H), 3.50 (s, 2H), 3.07-2.95 (m, 6H), 2.39 (m, 4H), 1.84-1.51 (m, 12H), 1.38-1.33 (m, 2H), 0.89 (t, 3H).

Workup

  1. temperaturewarmed to 23° C
  2. stirringwas then stirred at 20° C. for 30 min
  3. stirringstirring for 30 min
  4. temperaturethe suspension cooled to 3° C.
  5. stirringstirred for 1 hr
  6. filtrationThen the suspension was filtered
  7. customcollected solid
  8. washwashed with MTBE (15 g)
  9. customdried

Sources & evidence

ORD record
ord-9bce8d4f7f2841d59e58ffb5a08ce68f
Source dataset
uspto-grants-2014_11
Patent number
US08895570B2

Reaction notes

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