Ethanol → HCID 58504774, compound

HRID 2367629Notes

Reaction equation

HRID 2367629 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][C@H:21]([N:23]3CCO[C:24]3=[O:28])[CH2:20][C@@H:19]([CH3:29])[CH2:18]2)[N:3]=1.[CH2:30]([OH:32])[CH3:31].O.[NH2:34][NH2:35].[NH4+].[OH-]>C(Cl)Cl.CO>[NH2:1][C:2]1[N:3]=[C:4]([N:17]2[CH2:18][C@H:19]([CH3:29])[CH2:20][C@@H:21]([N:23]3[CH2:31][CH2:30][O:32][C:24]3=[O:28])[CH2:22]2)[CH:5]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:34][NH:35]3)=[CH:14][CH:15]=2)[N:7]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 14923Ammonium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 58504650HCID 58504650, compound

Product 1

HCID 58504774HCID 58504774, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
100 °C

Procedure

Into a 5 mL sealable vial were added 4-{2-amino-6-[(3R,5R)-3-methyl-5-(2-oxo-1,3-oxazolidin-3-yl)-1-piperidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (96 mg, 0.242 mmol) and ethanol (10 mL) followed by hydrazine monohydrate (0.356 mL, 7.27 mmol). The reaction vial was capped and was heated at 100° C. overnight. The reaction was concentrated, then dissolved in 2 mL of DMSO and purified on HPLC (HPLC condition: open-access Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 mL/min, 10% CH3CN/H2O, 0.1% TFA to 25% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced to remove most of the CH3CN. The water left behind was freeze dried, and the solid obtained was then dissolved in 2 mL of 9:1 CH2Cl2:CH3OH and then loaded on to a 10 g Biotage SNAP column. The product was then eluded off the column with a gradient of 0 to 100% 95:5:1 CH2Cl2:CH3OH:NH4OH in CH2Cl2 over 25 minutes. The product fractions were combined, concentrated, and then transferred into haystack vial. Water (1 mL) was added, and the resulting mixture was freeze dried to afford the title compound (55 mg) as a light yellow solid. LC-MS (ES) m/z=409 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.97 (d, J=6.6 Hz, 3H), 1.51-1.59 (m, 1H), 1.96 (ddd, J=12.8, 8.1, 4.4 Hz, 1H), 2.00-2.07 (m, 1H), 3.36-3.45 (m, 1H), 3.50-3.72 (m, 4H), 3.80-3.87 (m, 1H), 3.89-3.98 (m, 1H), 4.18-4.26 (m, 2H), 5.38 (s, 2H), 6.11 (s, 2H), 6.64 (s, 1H), 7.58 (dd, J=8.6, 1.3 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.95 (s, 1H), 11.51 (s, 1H).

Workup

  1. customThe reaction vial was capped
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in 2 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom7.3-minute
  6. customto remove most of the CH3CN
  7. waitThe water left behind
  8. customdried
  9. customthe solid obtained
  10. concentrationconcentrated
  11. additionWater (1 mL) was added
  12. customdried

Sources & evidence

ORD record
ord-ca74f46d3f584fe2af5f73229e6215e6
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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