Hydrazine → HCID 58865789, compound

HRID 1354825Notes

Reaction equation

HRID 1354825 reaction equation
[Cl:1][C:2]1[C:3]([N:42]2[CH2:47][C@@H:46]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][C@@H:44]([NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:43]2)=[N:4][C:5]([N:20]2[CH2:25][C@@H:24]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][C@@H:22]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:21]2)=[C:6]([Cl:19])[C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15]C(=O)C)=[CH:11][CH:10]=1.NN>CO.CN1C(=O)CCC1.CCOC(C)=O>[Cl:1][C:2]1[C:3]([N:42]2[CH2:47][C@@H:46]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][C@@H:44]([NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:43]2)=[N:4][C:5]([N:20]2[CH2:25][C@@H:24]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][C@@H:22]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:21]2)=[C:6]([Cl:19])[C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=1

Participants

6

Reactant 2

HCID 9321HydrazineHCID 58865774HCID 58865774, compound

Product 1

HCID 58865789HCID 58865789, compoundYield 89.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

N-[4-(3,5-dichloro-2,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-pyridin-4-ylamino)-phenyl]-acetamide (139) (0.849 g, 0.92 mmol) was dissolved in MeOH (5 mL) and NMP (10 mL). Hydrazine (10 mL) was added and the mixture was heated at 80° C. with shaking in a 40 mL I-Chem vial for 5 days. LC-MS at this point indicated nearly complete deprotection. The mixture was diluted with EtOAc (50 mL), washed with water (4×25 mL) and brine (25 mL) via extraction, dried over MgSO4 and concentrated to give a yellow oil. Purification by flash chromatography using a gradient of hexane and EtOAc (eluding with 15–100% EtOAc in hexane in 30 minutes) gave the desired product (140) as a beige powder upon concentration (0.728 g, 0.826 mmol, 89.8% yield). LC-MS (ESI): (exact mass: 879.42) m/e=880.5 [M+1]+ (100%).

Workup

  1. washwashed with water (4×25 mL) and brine (25 mL) via extraction
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customto give a yellow oil
  5. customPurification by flash chromatography
  6. customa gradient of hexane and EtOAc (eluding with 15–100% EtOAc in hexane in 30 minutes)

Sources & evidence

ORD record
ord-b6d772cba9f34cadb182b130908304ac
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

Loading…