Hydrochloric Acid → 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-piperazin-1-ylmethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 1402095Notes

Reaction equation

HRID 1402095 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[N:20]3[CH:21]=[C:22]([O:25][C@@H:26]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[C@H:29]([NH:36][C:37]([NH:39][C:40]5[N:41]([C:49]6[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=6)[N:42]=[C:43]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:44]=5)=[O:38])[CH2:28][CH2:27]4)[CH:23]=[CH:24][C:19]3=[N:18][N:17]=2)[CH2:11][CH2:10]1)=O)(C)(C)C>CO>[C:45]([C:43]1[CH:44]=[C:40]([NH:39][C:37]([NH:36][C@@H:29]2[C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:26]([O:25][C:22]3[CH:23]=[CH:24][C:19]4[N:20]([C:16]([CH2:15][N:12]5[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]5)=[N:17][N:18]=4)[CH:21]=3)[CH2:27][CH2:28]2)=[O:38])[N:41]([C:49]2[CH:50]=[CH:51][C:52]([CH3:55])=[CH:53][CH:54]=2)[N:42]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86686958HCID 86686958, compound

Product 1

HCID 716036671-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-piperazin-1-ylmethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

HCl (4M in dioxane; 1 mL) was added to a solution of Intermediate 7d (92 mg, 0.12 mmol) in MeOH (1 mL) at Rt and stirred for 4.5 h. The solution was loaded on to a SCX-2 cartridge, eluting with MeOH followed by 2M NH3 in MeOH, to give a pale yellow foam. Further purification by HPLC (40-80% MeCN in H2O (0.1% NH3)) gave the title compound as an off-white powder after freeze drying (28 mg, 35%). LCMS (Method 5): Rt 3.59 min, m/z 634 [MH+]. 1H NMR (400 MHz, CDCl3): 1.33 (9H, s), 1.89-1.98 (1H, m), 2.06-2.14 (2H, m), 2.25-2.32 (1H, m), 2.38 (3H, s), 2.38-2.48 (4H, m), 2.80-2.83 (4H, m), 4.03 (2H, s), 5.06-5.12 (1H, m), 5.20-5.24 (2H, m), 6.28 (1H, s), 6.34 (1H, br s), 7.08 (1H, dd, J 9.8, 2.0), 7.23-7.36 (6H, m), 7.40 (2H, d, J 7.7), 7.63 (1H, d, J 9.5), 8.14 (1H, m).

Workup

  1. washeluting with MeOH
  2. customto give a pale yellow foam
  3. customFurther purification by HPLC (40-80% MeCN in H2O (0.1% NH3))

Sources & evidence

ORD record
ord-d17b96ca3737456cb726cfc602e0cc08
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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