Aluminium lithium hydride → HCID 11683750, compound

HRID 1811563Notes

Reaction equation

HRID 1811563 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:33])=[N:25][C:26]([CH2:29][C:30](O)=[O:31])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:33])=[N:25][C:26]([CH2:29][CH2:30][OH:31])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 58671576HCID 58671576, compound

Product 1

HCID 11683750HCID 11683750, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-[6-(6-carboxymethyl-2-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (TFA salt, 582 mg, 1.01 mmol) in 4 mL THF was cooled in an ice-water bath and lithium aluminum hydride (ca 190 mg, 5 mmol) was added in small portions. After 2 h, mixture was quenched with ice-water; solids were filtered off, and washed with THF. Filtrate was concentrated and purified by HPLC. Fractions containing product were partly concentrated and residue was extracted with 1 M NaOH and methylene chloride. Organic phases were dried over MgSO4, filtered, and concentrated to give 4-{6-[6-(2-hydroxy-ethyl)-2-methyl-pyridin-3-ylamino]-5-methoxy-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester as a white solid (85.0 mg, 19%). 1HNMR (CDCl3, 400 MHz) δ 1.25-1.27 (d, J=6.2 Hz, 6H), 1.80-1.86 (m, 2H), 2.00-2.05 (m, 2H), 2.72 (s, 3H), 3.16-3.19 (t, J=5.6 Hz, 2H), 3.38-3.44 (m, 2H), 3.76-3.82 (m, 2H), 3.96-3.99 (t, J=5.6 Hz, 2H), 4.00 (s, 3H), 4.91-4.97 (m, 1H), 5.37-5.41 (m, 1H), 5.30 (s, 1H), 5.37-5.41 (m, 1H), 7.03 (s, 1H), 7.36-7.38 (d, J=8.5 Hz, 1H), 8.13 (s, 1H), 8.85 (s, 1H). Exact mass calculated for C22H31N5O5 445.23. found 446.1 (MH+).

Workup

  1. custommixture was quenched with ice-water
  2. filtrationsolids were filtered off
  3. washwashed with THF
  4. concentrationFiltrate was concentrated
  5. custompurified by HPLC
  6. additionFractions containing product
  7. concentrationwere partly concentrated
  8. extractionresidue was extracted with 1 M NaOH and methylene chloride
  9. dry with materialOrganic phases were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-61204e91d91244b2b40d129e663a47da
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

Loading…