Dimethylformamide → {4-[(Adamantan-1-ylmethyl)carbamoyl]pyrazolo[1,5-a]pyridin-2-ylmethoxy}acetic acid ethyl ester

HRID 2039780Notes

Reaction equation

HRID 2039780 reaction equation
C(O[K])(C)(C)C.[C:7]12([CH2:17][NH:18][C:19]([C:21]3[C:22]4[N:23]([N:27]=[C:28]([CH2:30][OH:31])[CH:29]=4)[CH:24]=[CH:25][CH:26]=3)=[O:20])[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][CH:9]([CH2:10]3)[CH2:8]1)[CH2:14]2.CN(C=O)C.Br[CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40]>C1COCC1>[CH2:42]([O:41][C:39](=[O:40])[CH2:38][O:31][CH2:30][C:28]1[CH:29]=[C:22]2[C:21]([C:19](=[O:20])[NH:18][CH2:17][C:7]34[CH2:8][CH:9]5[CH2:10][CH:11]([CH2:12][CH:13]([CH2:15]5)[CH2:14]3)[CH2:16]4)=[CH:26][CH:25]=[CH:24][N:23]2[N:27]=1)[CH3:43]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7748Ethyl bromoacetateHCID 25094828N-(adamantan-1-ylmethyl)-2-(hydroxymethyl)pyrazolo[1,5-a]pyridine-4-carboxamideHCID 178418922HCID 178418922, compound

Product 1

HCID 25095104{4-[(Adamantan-1-ylmethyl)carbamoyl]pyrazolo[1,5-a]pyridin-2-ylmethoxy}acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 1.0 M solution of tBuOK in THF (0.3 mL) is added to a mixture of 2-hydroxymethyl-pyrazolo[1,5-a]pyridine-4-carboxylic acid (adamantan-1-ylmethyl)amide (73 mg, 210 μmol) and DMF (1 mL) at 0° C. under N2. After 5 min, ethyl bromoacetate (30 μL, 280 μmol) is added. The cold bath is removed and the mixture is left to stir for 23 h. 50% Sat. aq. NaHCO3 is added and the solution is extracted with EtOAc (20 mL). The organics are dried over Na2SO4, filtered and concentrated. Purification by PTLC (2:1 EtOAc:hexanes) affords the title compound as a pale yellow film. 1H NMR (400 MHz, CDCl3) δ: 8.50 (dd, 1H), 7.57 (d, 1H), 6.88 (s, 1H), 6.81 (dt, 1H), 6.27 (bs, 1H), 4.88 (s, 2H), 4.22 (q, 2H), 4.19 (s, 2H), 3.21 (d, 2H), 1.94-2.04 (m, 3H), 1.56-1.78 (m, 12H), 1.28 (t, 3H). LC-MS m/z (M+H+): 426.3; RT=1.31.

Workup

  1. customThe cold bath is removed
  2. waitthe mixture is left
  3. addition50% Sat. aq. NaHCO3 is added
  4. extractionthe solution is extracted with EtOAc (20 mL)
  5. dry with materialThe organics are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by PTLC (2:1 EtOAc:hexanes)

Sources & evidence

ORD record
ord-074267c773944f40a8cb917b670fec2f
Source dataset
uspto-grants-2013_11
Patent number
US08580812B2

Reaction notes

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