Hydrochloric Acid → 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

HRID 662098Notes

Reaction equation

HRID 662098 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:28]=[C:27]([C:29]([O:31]C)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].O.[OH-].[Li+].Cl>O1CCCC1>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:28]=[C:27]([C:29]([OH:31])=[O:30])[CH:26]=[CH:25][CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 57819362methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate

Product 1

HCID 578193746-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acidYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate (32 g, 68.6 mmol) in a 1 L round-bottom flask under nitrogen in tetrahydrofuran (THF) (600 mL) was added water (150 mL), then lithium hydroxide (2.464 g, 103 mmol). After 22 min the slightly cloudy mixture was filtered and the THF was evaporated off to give a slight suspension. The aqueous mixture was cooled in an ice-bath and taken to pH 6 using 2M hydrochloric acid. This mixture was stirred for 10 min in an ice-bath, the pH re-checked but not much material seemed to have come out of solution. So the pH was further reduced to pH 5 and this seemed to bring more material out of solution. The solid was collected by vacuum filtration, washed with water then dried under high vacuum at 40° C. to give 19.2 g (62%) of a white solid that the Lab HPLC showed to be 98.7% pure with a retention time of 1.76 min. LC-MS m/z 453 (M+H)+, 0.72 min (ret time) [split peak].

Workup

  1. filtrationAfter 22 min the slightly cloudy mixture was filtered
  2. customthe THF was evaporated off
  3. customto give a slight suspension
  4. temperatureThe aqueous mixture was cooled in an ice-bath
  5. filtrationThe solid was collected by vacuum filtration
  6. washwashed with water
  7. customthen dried under high vacuum at 40° C.

Sources & evidence

ORD record
ord-1014591a84e049169cc472d56f444583
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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