Hydrazine → HCID 58504628, compound

HRID 2367630Notes

Reaction equation

HRID 2367630 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:29])[NH:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[CH:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21](F)[CH:20]=3)[N:16]=[C:15]([NH2:28])[N:14]=2)[CH2:8]1)[CH3:3].[NH2:30][NH2:31]>C(O)C>[CH3:3][CH:2]([O:4][C:5](=[O:29])[NH:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[CH:18]=[C:17]([C:19]3[CH:24]=[C:23]4[C:22]([C:25]([NH2:26])=[N:30][NH:31]4)=[CH:21][CH:20]=3)[N:16]=[C:15]([NH2:28])[N:14]=2)[CH2:8]1)[CH3:1]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 58504509HCID 58504509, compound

Product 1

HCID 58504628HCID 58504628, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

Into a 5 mL sealable vial was added 1-methylethyl{(3R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-3-piperidinyl}carbamate (116 mg, 0.291 mmol) followed by ethanol (3 mL) and hydrazine (0.428 mL, 8.73 mmol). The mixture was then capped and 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 35% 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. To the water left behind was added saturated NaHCO3. It was then extracted with EtOAc (3×15 mL) and the organic fractions were combined and washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The product was then transferred to a haystack vial and 1 mL of water was added and freeze dried. LC-MS (ES) m/z=411 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (d, 3H), 1.16 (d, J=6.3 Hz, 3H), 1.39-1.49 (m, 2H), 1.70-1.77 (m, 1H), 1.85-1.93 (m, 1H), 2.87 (bs, 1H), 3.03 (bs, 1H), 4.06-4.16 (m, 1H), 4.28 (bs, 1H), 4.77 (ddd, J=12.51, 6.19, 6.06 Hz, 1H), 5.38 (s, 2H), 6.09 (bs, 2H), 6.56 (s, 1H), 7.16 (d, J=7.6 Hz, 1H), 7.54 (d, J=8.6 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.92 (s, 1H), 11.52 (s, 1H).

Workup

  1. customThe mixture was then 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. waitTo the water left behind
  8. additionwas added saturated NaHCO3
  9. extractionIt was then extracted with EtOAc (3×15 mL)
  10. washwashed with saturated NaCl solution
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionwas added
  15. customfreeze dried

Sources & evidence

ORD record
ord-013150e2dd6a4f8bafb3018af71af6c5
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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