Potassium Phosphate, Tribasic → HCID 86617878, compound

HRID 2426810Notes

Reaction equation

HRID 2426810 reaction equation
[Cl-].[CH3:2][C@H:3]1[CH2:5][C@@H:4]1[C@@H:6]([NH3+:8])[CH3:7].Cl[C:10]1[CH:15]=[C:14]([C:16]2[O:17][C:18]([C@@:21]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:29])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][N:20]=2)[CH:13]=[C:12]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:41])=[O:40])[N:11]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:29][C@:21]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])([C:18]1[O:17][C:16]([C:14]2[CH:13]=[C:12]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:41])=[O:40])[N:11]=[C:10]([NH:8][C@H:6]([C@H:4]3[CH2:5][C@@H:3]3[CH3:2])[CH3:7])[CH:15]=2)=[N:20][CH:19]=1)[CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 59651100HCID 59651100, compound2×HCID 67253137HCID 67253137, compound2×

Product 1

HCID 86617878HCID 86617878, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (1S)-1-[(1S,2S)-2-methylcyclopropyl]ethanaminium chloride (intermediate P, 0.039 g, 0.29 mmol) and tert-butyl (1R)-1-(2-{2-chloro-6-[methyl(methylsulfonyl)amino]pyridin-4-yl}-1,3-oxazol-5-yl)-1-methyl-2-phenylethylcarbamate (intermediate k, 0.050 g, 0.10 mmol) in 1 mL DMF was added K3PO4 (0.122 g, 0.58 mmol) and Pd(PtBu3)2 (0.007 g, 0.01 mmol). After 16 h at ambient temperature, the sealed reaction was heated at 110° C. for 8.5 h and then filtered over a pad of celite. The celite was washed with EtOAc (60 mL). The filtrate was concentrated in vacuo and the resulting residue taken up in DMF and purified by reverse phase LC. The resulting material was diluted with EtOAc (40 mL) and washed with saturated sodium bicarbonate solution (20 mL). The aqueous layer was back extracted with EtOAc (20 mL). The combined organics were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo to give 0.028 g (50%) of tert-butyl (1R)-1-methyl-1-(2-{2-({(1S)-1-[(1S,2S)-2-methylcyclopropyl]ethyl}amino)-6-[methyl(methylsulfonyl)amino]pyridin-4-yl}-1,3-oxazol-5-yl)-2-phenylethylcarbamate as a yellow residue. (CDCl3, 400 MHz) 7.28 (m 3H); 7.06 (d, J=0.91 Hz, 1H); 7.03 (m, 2H); 6.93 (s, 1H); 6.76 (s, 1H); 3.50 (m, 1H); 3.36 (m, 4H); 14 (m, 4H); 1.60 (s, 3H); 1.42 (s, 9H); LC/MS [M+H]+=584.

Workup

  1. customthe sealed reaction
  2. filtrationfiltered over a pad of celite
  3. washThe celite was washed with EtOAc (60 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by reverse phase LC
  6. additionThe resulting material was diluted with EtOAc (40 mL)
  7. washwashed with saturated sodium bicarbonate solution (20 mL)
  8. extractionThe aqueous layer was back extracted with EtOAc (20 mL)
  9. washThe combined organics were washed with brine (20 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bab334af75ad4a5999537704b7f17d4e
Source dataset
uspto-grants-2011_06
Patent number
US07968571B2

Reaction notes

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