Ammonium formate → HCID 20764011, compound

HRID 983422Notes

Reaction equation

HRID 983422 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:33])[CH2:9][NH:10][CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:21]=[C:22]([CH2:25][C:26]([N:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[O:27])[O:23][CH:24]=3)=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.C(OCC)C.[Pd]>[OH:33][C@H:8]([C:5]1[CH:6]=[N:7][CH:2]=[CH:3][CH:4]=1)[CH2:9][NH:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[N:21]=[C:22]([CH2:25][C:26]([N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:27])[O:23][CH:24]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 20764010HCID 20764010, compound

Product 1

HCID 20764011HCID 20764011, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

In a nitrogen-purged, round-bottomed flask, (R)-2-[4-(4-{2-[2-(6-chloro-pyridin-3-yl)-2-hydroxy-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-1-pyrrolidin-1-yl-ethanone 1-1A (200 mg, 0.42 mmol) was dissolved in methanol (15 ml). 10% Pd/C (160 mg, 80 wt %), and ammonium formate (321 mg, 5.1 mmol) were then added sequentially. The reaction mixture was stirred overnight, and was then filtered through a pad of diatomaceous earth, and the filter cake rinsed with ethyl acetate. The filtrate was concentrated to a white solid, which was taken up in ethyl acetate and saturated aqueous sodium carbonate, and extracted. The organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a crude solid. This material was suspended in diethylether and isolated by vacuum filtration to afford a crystalline solid 1-1B (110 mg, 59% yield). This material was then converted to the corresponding hydrochloride salt. Analytical data for the HCl salt: LRMS ([M+H]+): 437.4. 1H NMR: (400 MHz, CD3OD): δ1.91 (m, 2H), 2.02 (m, 2H), 3.37-3.29 (m, 2H), 3.45 (m, 2H), 3.54-3.63 (m, 5H), 3.97 (s, 2H), 4.37 (t, 2H, J=4.8 Hz), 5.38 (dd, 1H, J=3.2,10.4 Hz), 7.07 (dd, 2H, J=2.8, 9.6 Hz), 7.69 (dd, 2H, J=1.8, 6.4 Hz), 8.14 (m, 2H), 8.75 (m, 1H), 8.86 (d, 1H, J=6.0 Hz), 8.99 (m, 1H). Preparation for 2-[4-(4-{2-[2(R)-Hydroxy-2-(6-methyl-pyridin-3-yl)-ethylamino]-ethoxy}-phenyl)-oxazol-2-yl]-N,N-dimethyl-acetamide (1-1C)

Workup

  1. customIn a nitrogen-purged
  2. filtrationwas then filtered through a pad of diatomaceous earth
  3. washthe filter cake rinsed with ethyl acetate
  4. concentrationThe filtrate was concentrated to a white solid, which
  5. extractionsaturated aqueous sodium carbonate, and extracted
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford a crude solid
  11. customisolated by vacuum filtration

Sources & evidence

ORD record
ord-e85f25e5ba0743c3897988a9c5b662a1
Source dataset
uspto-grants-2005_03
Patent number
US06864268B2

Reaction notes

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