HCID 86636970, compound → HCID 58000526, compound

HRID 1366516Notes

Reaction equation

HRID 1366516 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH:9][C:10](=[O:29])[C@H:11]([CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:12][N:13]([O:16]C2CCCCO2)[CH:14]=[O:15])[C:5]([F:30])=[C:4]([N:31]2[CH2:37][CH:36]([N:38]([CH3:40])[CH3:39])[C:33]3([CH2:35][CH2:34]3)[CH2:32]2)[N:3]=1>CC(O)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH:9][C:10](=[O:29])[C@H:11]([CH2:23][CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28]2)[CH2:12][N:13]([OH:16])[CH:14]=[O:15])[C:5]([F:30])=[C:4]([N:31]2[CH2:37][CH:36]([N:38]([CH3:40])[CH3:39])[C:33]3([CH2:35][CH2:34]3)[CH2:32]2)[N:3]=1

Participants

3

Reactant 1

HCID 86636970HCID 86636970, compound

Product 1

HCID 58000526HCID 58000526, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 21899381Acetic acid--water (1/1)Solvent

Procedure

A solution of [(2R)-3-(2-{2-chloro-6-[7-(dimethylamino)-5-azaspiro[2.4]hept-5-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (0.0961 g, 0.165 mmol) in 4:1 HOAc-water (5 mL) was stirred for 3 days. The solution was concentrated in vacuo and diluted with DCM (100 mL). The solution was washed with sat. aq. NaHCO3 (25 mL), and the organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by Gilson RPLC, and the desired fractions were concentrated in vacuo and azeotroped first with MeOH and then with EtOAc. The residue was crystallized from EtOAc-hexanes to provide [(2R)-3-(2-{2-chloro-6-[7-(dimethylamino)-5-azaspiro[2.4]hept-5-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl]hydroxyformamide (0.0469 g, 57%, mixture of diastereomers) as a white solid. LCMS: (M+H)+: 498.1.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. additiondiluted with DCM (100 mL)
  3. washThe solution was washed with sat. aq. NaHCO3 (25 mL)
  4. dry with materialthe organic phase was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Gilson RPLC
  8. concentrationthe desired fractions were concentrated in vacuo
  9. customazeotroped first with MeOH
  10. customThe residue was crystallized from EtOAc-hexanes

Sources & evidence

ORD record
ord-9cb6f6e0e71c4a8aa4415ae87a23c4a4
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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