3-{6-[2-(2-Chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester → 2-[4-(5-Azetidin-3-yl-pyridin-2-ylamino)-7-fluoropyrazolo[4,3-c]pyridin-2-yl]-3-chlorobenzonitrile hydrochloride salt

HRID 626762Notes

Reaction equation

HRID 626762 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([C:12]2[CH:13]=[N:14][C:15]([NH:18][C:19]3[C:24]4=[CH:25][N:26]([C:28]5[C:33]([C:34]#[N:35])=[CH:32][CH:31]=[CH:30][C:29]=5[Cl:36])[N:27]=[C:23]4[C:22]([F:37])=[CH:21][N:20]=3)=[CH:16][CH:17]=2)[CH2:9]1)=O)(C)(C)C>Cl>[ClH:36].[NH:8]1[CH2:9][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]3[C:24]4=[CH:25][N:26]([C:28]5[C:29]([Cl:36])=[CH:30][CH:31]=[CH:32][C:33]=5[C:34]#[N:35])[N:27]=[C:23]4[C:22]([F:37])=[CH:21][N:20]=3)=[N:14][CH:13]=2)[CH2:11]1

Participants

3

Reactant 1

HCID 696749593-{6-[2-(2-Chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866970672-[4-(5-Azetidin-3-yl-pyridin-2-ylamino)-7-fluoropyrazolo[4,3-c]pyridin-2-yl]-3-chlorobenzonitrile hydrochloride salt

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a round bottomed flask containing 3-{6-[2-(2-chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester (98 mg, 0.19 mmol), was added a solution of HCl (1.25 N in propan-2-ol, 10 mL) and the suspension was stirred at room temperature for 16 hours and then heated at 50° C. for 4 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and the resultant solid was triturated with diethyl ether, filtered and dried. The crude residue obtained was purified by HPLC [gradient: 20 to 98% MeOH (0.1% NH4OH) in water (0.1% NH4OH)] and freeze dried to afford the free base of the title compound which was dissolved in a solution of HCl (1.25 N in propan-2-ol, 5.0 mL), stirred for 4 hours and was then concentrated under reduced pressure. The resultant residue was triturated with diethyl ether, filtered and dried to yield the title compound as a white solid (30 mg, 35% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.00 (d, J=2.5 Hz, 1H), 8.50 (d, J=2.5 Hz, 1H), 8.31 (dd, J=8.7, 2.5 Hz, 1H), 8.26-8.22 (m, 2H), 8.18 (d, J=4.9 Hz, 1H), 7.96 (t, J=8.1 Hz, 1H), 7.75 (d, J=8.9, 1H), 4.39-4.28 (m, 3H), 4.24-4.14 (m, 2H). LCMS (Method B): RT=2.29 min, m/z: 420 [M+H+].

Workup

  1. temperatureheated at 50° C. for 4 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customthe resultant solid was triturated with diethyl ether
  5. filtrationfiltered
  6. customdried
  7. customThe crude residue obtained
  8. customwas purified by HPLC [gradient: 20 to 98% MeOH (0.1% NH4OH) in water (0.1% NH4OH)] and freeze
  9. customdried

Sources & evidence

ORD record
ord-708a57c9f1554b3a93f2a6166d4b3e02
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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