Hydrochloric Acid → HCID 57387900, compound

HRID 1529376Notes

Reaction equation

HRID 1529376 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15](C3CCCCO3)[N:14]=[C:13]4[C:25]3[N:30]=[C:29]([NH:31][C@@H:32]4[CH2:37][CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33]4)[CH:28]=[N:27][CH:26]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.Cl>CO>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[NH:15][N:14]=[C:13]4[C:25]3[N:30]=[C:29]([NH:31][C@@H:32]4[CH2:37][CH2:36][CH2:35][NH:34][CH2:33]4)[CH:28]=[N:27][CH:26]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67959657HCID 67959657, compound

Product 1

HCID 57387900HCID 57387900, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (3R)-tert-butyl 3-(6-(5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (179 mg, 0.30 mmol) and HCl (5-6 M in IPA, 6.00 mL, 30.0 mmol) in 4 mL of MeOH was heated at 80° C. for 90 min. The crude reaction was cooled to RT and concentrated to a yellow solid that was slurried with a 1\1 mixture of DCM\MeOH (12 mL) and applied to a pre-washed (45 mL MeOH) of Si-propylsulfonic acid (12 g, Silicycle, Cat# R51230B). The column was washed with MeOH (35 mL). The compound was released with 35 mL of 2 M NH3 in MeOH to afford 120 mg of crude material, which was purified by HPLC (5-100% MeCN in H2O with 0.1% TFA over 15 min) to afford the title compound (56 mg, 0.14 mmol, 45% yield) as a pale yellow solid. MS (ESI, pos. ion) m/z: 413.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.15 (s, 2H), 8.55 (s, 1H), 8.47 (s, 1H), 8.16 (dd, J=8.80, 1.76 Hz, 1H), 7.95 (s, 1H), 7.75 (d, J=8.80 Hz, 1H), 7.13 (d, J=7.63 Hz, 1H), 4.03-4.16 (m, 1H), 3.14-3.25 (m, 1H), 2.78-2.87 (m, 1H), 2.53-2.62 (m, 2H), 2.30 (quin, J=6.41 Hz, 1H), 2.00-2.08 (m, 1H), 1.66-1.77 (m, 1H), 1.46-1.63 (m, 2H), 1.05-1.16 (m, 4H).

Workup

  1. customThe crude reaction
  2. concentrationconcentrated to a yellow solid
  3. additionthat was slurried with a 1\1 mixture of DCM\MeOH (12 mL)
  4. washa pre-washed (45 mL MeOH) of Si-propylsulfonic acid (12 g, Silicycle, Cat# R51230B)
  5. washThe column was washed with MeOH (35 mL)
  6. customto afford 120 mg of crude material, which
  7. customwas purified by HPLC (5-100% MeCN in H2O with 0.1% TFA over 15 min)

Sources & evidence

ORD record
ord-d14f2a49d73d409daeed4b4caaa9ecd3
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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