Hydrochloric Acid → 3-(5-Fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine

HRID 1926443Notes

Reaction equation

HRID 1926443 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:36])=[C:23]([N:25]4[CH2:34][CH2:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][C:31]=5[F:35])[CH2:26]4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>CO.CCOCC>[F:35][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:32]=1[CH2:33][CH2:34][N:25]([C:23]1[C:22]([NH2:36])=[N:21][CH:20]=[C:19]([C:17]3[CH:16]=[N:15][N:14]([CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH:18]=3)[CH:24]=1)[CH2:26]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67521077HCID 67521077, compound

Product 1

HCID 675209183-(5-Fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

4-{4-[6-Amino-5-(5-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (34 mg) was dissolved in MeOH (20 mL), 1.0 M of HCl in Et2O (20 mL) was added, and the mixture was stirred at rt overnight. The solvent was removed in vacuo to give a brown oil. It was purified by Gilson HPLC eluting with H2O/CH3CN/0.1% formic acid mixtures to give the title compound contaminated with the corresponding formamide. This material was dissolved in MeOH (2 ml), aqueous NaOH (10 N, 2 ml) was added, and the solution was stirred at rt overnight. It was then treated with water (5 ml) and extracted with DCM (3×20 ml). The extracts were washed with water (2×20 ml), brine (20 ml), dried over MgSO4, filtered, and concentrated in vacuo, to give the title compound as a beige solid. 1H NMR (400 MHz, CD3OD): δ=1.79-1.92 (m, 2H), 1.98-2.06 (m, 2H), 2.63-2.70 (m, 2H), 2.90 (t, J=6.0 Hz, 2H), 3.06-3.14 (m, 2H), 3.18-3.24 (m, 2H), 4.06 (s, 2H), 4.15-4.23 (m, 1H), 6.82 (d, J=8.8 Hz, 1H), 6.85-6.88 (m, 1H), 7.05-7.12 (m, 1H), 7.44 (d, J=2.4 Hz, 1H), 7.66 (d, J=0.8 Hz, 1H), 7.83 (d, J=2.0 Hz, 1H), 7.91 (d, J=0.4 Hz, 1H). MS(ES+): m/z=394.14 (45) [MH+]. HPLC: tR=2.21 min (ZQ2, polar—5 min).

Workup

  1. customThe solvent was removed in vacuo
  2. customto give a brown oil
  3. customIt was purified by Gilson HPLC
  4. washeluting with H2O/CH3CN/0.1% formic acid

Sources & evidence

ORD record
ord-17e8d275c6d9403094da8f146174aea9
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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