Acetic Acid → ethyl 5-methoxy-1-(5-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)pyridin-2-yl)-1H-pyrazole-4-carboxylate

HRID 578926Notes

Reaction equation

HRID 578926 reaction equation
[OH:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13](=[O:22])[NH:14][CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24].[CH3:28]COC(C)=O.[N+](=C[Si](C)(C)C)=[N-].C(O)(=O)C>CO>[CH3:28][O:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13](=[O:22])[NH:14][CH2:15][CH:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 167693TrimethylsilyldiazomethaneHCID 178469979HCID 178469979, compound

Product 1

HCID 117600311ethyl 5-methoxy-1-(5-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)pyridin-2-yl)-1H-pyrazole-4-carboxylateYield 65.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

Combined ethyl 5-hydroxy-1-(5-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)pyridin-2-yl)-1H-pyrazole-4-carboxylate (0.6 g, 1.603 mmol), EtOAc (30 mL), and MeOH (10 mL) then added (diazomethyl)trimethylsilane, 2.0 M solution in hexanes (2.60 mL, 5.21 mmol) at 23° C. over 20 minutes. The reaction mixture was stirred at 23° C. for 1 hour, quenched with acetic acid (0.206 mL, 3.61 mmol), and the mixture was stirred for 2 hours at 23° C. The reaction mixture was concentrated to give an orange-brown oil which was purified by medium pressure chromatography using an eluent of 100% EtOAc on a 25 g silica gel column (Single Step™) to give the title compound (408 mg, 65.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.27 (m, 2 H) 1.31 (t, J=7.07 Hz, 3 H) 1.62 (dd, J=12.88, 2.02 Hz, 2 H) 1.81 (ttd, J=11.13, 11.13, 7.31, 7.31, 3.79 Hz, 1 H) 3.20 (t, J=6.44 Hz, 2 H) 3.27 (td, J=11.68, 2.15 Hz, 2 H) 3.85 (dt, J=9.35, 2.27 Hz, 2 H) 4.14 (s, 3 H) 4.27 (q, J=7.07 Hz, 2 H) 7.79 (dd, J=8.34, 0.76 Hz, 1 H) 8.03 (s, 1 H) 8.38-8.43 (m, 1 H) 8.78 (t, J=5.81 Hz, 1 H) 8.98 (dd, J=2.53, 0.76 Hz, 1 H). MS m/z [M+H]+ 389.4.

Workup

  1. stirringthe mixture was stirred for 2 hours at 23° C
  2. concentrationThe reaction mixture was concentrated
  3. customto give an orange-brown oil which
  4. customwas purified by medium pressure chromatography

Sources & evidence

ORD record
ord-463aeef947294133b01802c4709eed10
Source dataset
uspto-grants-2015_05
Patent number
US09040522B2

Reaction notes

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