Hydrochloric Acid → 3-(4-Fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

HRID 1926251Notes

Reaction equation

HRID 1926251 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]([C:25]4[N:26]=[CH:27][C:28]5[C:33]([C:34]=4[F:35])=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(Cl)[Cl:38].[ClH:40].CCOCC>>[ClH:38].[ClH:40].[ClH:38].[F:35][C:34]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[N:26][C:25]=1[C:23]1[C:22]([NH2:36])=[N:21][CH:20]=[C:19]([C:17]2[CH:16]=[N:15][N:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:18]=2)[CH:24]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6344DichloromethaneHCID 675203744-{4-[6-Amino-5-(4-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 675205253-(4-Fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

Procedure

To a solution of 4-{4-[6-amino-5-(4-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (16.0 mg, 0.0327 mmol) in DCM (0.60 mL, 9.4 mmol) was added 1.0 M of HCl in Et2O (0.90 mL, 0.90 mmol), and the mixture was stirred at ambient temperature for 2 h. Almost immediately a pale yellow solid precipitated. The solvents were evaporated, and the residue was transferred into a vial and dried in vacuo overnight, yielding the title compound as pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=14.6 (very brs, 1H), 9.38 (s, 1H), 9.08-8.99 (brm, 1H), 8.91-8.80 (brm, 1H), 8.53 (brs, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.40 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.24 (dd, J=8.2, 0.8 Hz, 1H), 8.06 (d, J=0.4 Hz, 1H), 8.03 (ddd, J=0.8, 7.0, 8.2 Hz, 1H), 7.92 (ddd, J=1.0, 7.0, 8.2 Hz, 1H), 7.88 (brs, 1H), 4.54-4.45 (mc, 1H), 3.38 (brd, J=13.2 Hz, 2H), 3.09 (brq, J=11.6 Hz, 2H), 2.27-2.08 (m, 4H). MS(ES+): m/z=389.18 (18) [MH+], 306.13 (100) [MH+-piperidine]. HPLC: tR=1.69 min (polar—5 min, ZQ2).

Workup

  1. customAlmost immediately a pale yellow solid precipitated
  2. customThe solvents were evaporated
  3. customdried in vacuo overnight

Sources & evidence

ORD record
ord-19d8102e41224dee81873bd9b07c5bf1
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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