Hydrochloric Acid → 3-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide

HRID 217787Notes

Reaction equation

HRID 217787 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][N:26]([CH2:34][CH2:35][CH2:36][O:37][CH3:38])C(=O)OC(C)(C)C)=[CH:19][CH:18]=2)=[N:6][C:7]=1[C:8](=[O:16])[NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1.Cl.[OH-].[Na+].CC1CCCO1>O>[NH2:1][C:2]1[C:7]([C:8]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[O:16])=[N:6][C:5]([C:17]2[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][CH2:25][NH:26][CH2:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:21][CH:22]=2)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 73012-MethyltetrahydrofuranHCID 14798Sodium Hydroxide2×HCID 66678170Tert-butyl (3-{4-[5-amino-6-(pyridin-3-ylcarbamoyl)pyrazin-2-yl]phenyl}propyl)(3-methoxypropyl)carbamate

Product 1

HCID 533023753-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Tert-butyl (3-{4-[5-amino-6-(pyridin-3-ylcarbamoyl)pyrazin-2-yl]phenyl}propyl)(3-methoxypropyl)carbamate (1 kg) and water (8 L) were added to the reactor, stirred and heated up to 70° C. 36% Hydrochloric acid (606 ml) was added slowly controlling rate of gas evolution. The contents were stirred for 45 minutes at 70° C. The pH was adjusted to 3-4 by addition of sodium hydroxide (325 ml). The contents were cooled to 50° C. and 2-methyltetrahydrofuran (5 L) was added. The pH was then adjusted to pH 11-12 by the addition of 48% sodium hydroxide liquor (170 ml). The contents were then cooled to 40° C. The batch allowed to settle and the two layers separated. The aqueous layer was washed with 2-methyltetrahydrofuran (2.5 L). The combined organic layers were washed with a solution of 10% w/v aqueous sodium chloride solution. The organic layer was distilled to remove 3.75 L of distillate. The remaining liquors were heated to 50° C. and methyl-t-butyl ether (4 L) added. The liquors were cooled to 10° C. over 4 hours then isolated by filtration. The solid was washed with methyl-t-butyl ether (2 L×2) and dried in a vacuum oven at 50° C. 3-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide (721 g).

Workup

  1. stirringThe contents were stirred for 45 minutes at 70° C
  2. temperatureThe contents were cooled to 50° C.
  3. temperatureThe contents were then cooled to 40° C
  4. customthe two layers separated
  5. washThe aqueous layer was washed with 2-methyltetrahydrofuran (2.5 L)
  6. washThe combined organic layers were washed with a solution of 10%
  7. distillationThe organic layer was distilled
  8. customto remove 3.75 L of distillate
  9. temperatureThe remaining liquors were heated to 50° C.
  10. additionmethyl-t-butyl ether (4 L) added
  11. temperatureThe liquors were cooled to 10° C. over 4 hours
  12. customthen isolated by filtration
  13. washThe solid was washed with methyl-t-butyl ether (2 L×2)
  14. customdried in a vacuum oven at 50° C

Sources & evidence

ORD record
ord-41f8db4c6a8d4103a0afe7a118986c30
Source dataset
uspto-grants-2012_06
Patent number
US08198285B2

Reaction notes

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