Hydroxyamine hydrochloride → HCID 60126011, compound

HRID 422967Notes

Reaction equation

HRID 422967 reaction equation
Cl.[NH2:2][OH:3].C[O-].[Na+].[C:7]([O:11][C:12]([NH:14][CH2:15][C@H:16]([NH:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([C:30]#[C:31][C:32]2[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:49])[CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[CH:34][CH:33]=2)=[CH:26][CH:25]=1)=[O:23])[C:17]([O:19]C)=O)=[O:13])([CH3:10])([CH3:9])[CH3:8]>CO.C1COCC1.C(Cl)(Cl)Cl.CC(O)C>[OH:3][NH:2][C:17]([C@@H:16]([NH:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([C:30]#[C:31][C:32]2[CH:33]=[CH:34][C:35]([NH:38][C:39](=[O:49])[CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:46])[CH3:47])=[O:43])=[CH:36][CH:37]=2)=[CH:26][CH:25]=1)=[O:23])[CH2:15][NH:14][C:12]([O:11][C:7]([CH3:9])([CH3:8])[CH3:10])=[O:13])=[O:19]

Participants

7

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 58991104HCID 58991104, compound

Product 1

HCID 60126011HCID 60126011, compoundYield 64.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of hydroxylamine hydrochloride (98 mg, 1.41 mmol) in MeOH (1.3 mL) at 0° C. was added 25 wt % NaOMe (460 mg, 2.13 mmol). The solution was stirred at 0° C. for 15 min and then charged with a solution of methyl (2S)-3-[(tert-butoxy)carbonylamino]-2-({4-[2-(4-{2-[(tert-butoxy)carbonylamino]acetylamino}phenyl)ethynyl]phenyl}carbonylamino)propanoate (4) (279 mg, 0.469 mmol) in THF (1.5 mL) and MeOH (0.6 mL). The reaction was stirred at 0° C. for 30 min and at room temperature for 2.5 h. The reaction mixture was diluted with 4:1 CHCl3/iPrOH (50 ml) and washed with 0.1 M HCl (30 mL). The layers were separated and the aqueous layer extracted once more with 4:1 CHCl3/iPrOH (30 ml). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The crude residue was suspended in 10:1 CH2Cl2/MeOH (4 mL), filtered, and washed with 50:1 CH2Cl2/MeOH (2 mL) and Et2O (10 mL) to afford 180 mg (64%) of N-(4-{2-[4-(N-{1-(N-hydroxycarbamoyl)(1S)-2-[(tert-butoxy)carbonylamino]ethyl}carbamoyl) phenyl]ethynyl}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide (6) as a white powder.

Workup

  1. stirringThe reaction was stirred at 0° C. for 30 min and at room temperature for 2.5 h
  2. washwashed with 0.1 M HCl (30 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted once more with 4:1 CHCl3/iPrOH (30 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. filtrationfiltered
  9. washwashed with 50:1 CH2Cl2/MeOH (2 mL) and Et2O (10 mL)

Sources & evidence

ORD record
ord-c5056d1d06d34d289f2db05ea98b91f6
Source dataset
uspto-grants-2012_01
Patent number
US08101640B2

Reaction notes

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