Hydrazine → HCID 58504458, compound

HRID 2367422Notes

Reaction equation

HRID 2367422 reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:34])[NH:10][C@H:11]2[CH2:16][CH2:15][C@@H:14]([CH3:17])[N:13]([C:18]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=4)[N:21]=[C:20]([NH2:33])[N:19]=3)[CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:35][NH2:36]>C(O)C>[C:1]1([CH2:7][O:8][C:9](=[O:34])[NH:10][C@H:11]2[CH2:16][CH2:15][C@@H:14]([CH3:17])[N:13]([C:18]3[CH:23]=[C:22]([C:24]4[CH:25]=[C:26]5[C:27]([C:30]([NH2:31])=[N:35][NH:36]5)=[CH:28][CH:29]=4)[N:21]=[C:20]([NH2:33])[N:19]=3)[CH2:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 58504609HCID 58504609, compound

Product 1

HCID 58504458HCID 58504458, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To phenylmethyl{(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-3-piperidinyl}carbamate (57 mg, 0.124 mmol) in ethanol (3 mL) was added hydrazine (0.182 mL, 3.71 mmol) into a 5 mL sealable vial. The solution was then capped and heated at 100° C. overnight. The reaction was then concentrated, re-dissolved in 2 mL of DMSO, and purified on HPLC (HPLC condition: open-access Gilson using Unipoint software with a Varian Polaris 5u C18(2) 100A, 50×30.00 mm 5 micron. 10-minute run (30 ml/min, 33% CH3CN/H2O, 0.1% TFA to 58% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined, and the volume was reduced to remove the CH3CN. To the resulting aqueous mixture was added 5 mL of saturated aqueous NaHCO3, and then extracted 3× with EtOAc. The organics were then combined, washed with brine, dried over MgSO4, filtered and concentrated to afford the title compound (37 mg) as a light yellow solid. LC-MS (ES) m/z=473 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.12 (d, J=6.8 Hz, 3H), 1.66 (m, 4H), 2.67 (dt, J=3.7, 1.8 Hz, 1H), 3.38 (bs, 1H), 4.50 (bs, 1H), 4.73 (bs, 1H), 5.06 (d, J=5.3 Hz, 2H), 5.39 (s, 2H), 6.04-6.20 (bs, 2H), 6.58 (bs, 1H), 7.30-7.46 (m, 6H), 7.55 (d, J=8.3 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.93 (s, 1H), 11.52 (bs, 1H).

Workup

  1. customThe solution was then capped
  2. concentrationThe reaction was then concentrated
  3. dissolutionre-dissolved in 2 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom10-minute
  6. customto remove the CH3CN
  7. additionTo the resulting aqueous mixture was added 5 mL of saturated aqueous NaHCO3
  8. extractionextracted 3× with EtOAc
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-a7f1633f96684f188fc5f7b7e79e7b73
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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