Water → HCID 71060537, compound

HRID 1036690Notes

Reaction equation

HRID 1036690 reaction equation
[NH2:1][C@H:2]([CH2:23][O:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([CH3:13])[CH2:9][CH:8]2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6]1)=[O:4].O=C1CCC(=O)N1[O:40][C:41](=O)[C:42]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH3:44])[CH3:43].O>C1COCC1>[C:49]([O:48][C:46](=[O:47])[NH:45][C:42]([C:41](=[O:40])[NH:1][C@H:2]([CH2:23][O:24][CH2:25][C:26]1[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=1)[C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([CH3:13])[CH2:9][CH:8]2[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:6]1)=[O:4])([CH3:44])[CH3:43])([CH3:52])([CH3:50])[CH3:51]

Participants

5

Reactant 3

HCID 962WaterHCID 22557098HCID 22557098, compoundHCID 71060581HCID 71060581, compound

Product 1

HCID 71060537HCID 71060537, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 7-[(R)-2-Amino-3-(4-fluoro-benzyloxy)-propionyl]-2-methyl-4-phenyl-2,7-diaza-spiro[4.5]decan-1-one (130 mg, 0.3 mmol) (step 2) and 2-tert-Butoxycarbonylamino-2-methyl-propionic acid 2,5-dioxo-pyrrolidin-1-yl ester (synthesis described in EP1486498A1 page 20) (89 mg, 0.3 mmol) in THF (4 ml)/water (1 ml) was treated with TEA (0.12 ml, 0.89 mmol). The resulting mixture was stirred at 50° C. for 6 h. The reaction mixture was concentrated in vacuo and the residue partitioned between EtOAc (25 ml) and 5% citric acid aqueous solution (10 ml). The organic phase was separated, washed with brine (10 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane to afford the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between EtOAc (25 ml) and 5% citric acid aqueous solution (10 ml)
  3. customThe organic phase was separated
  4. washwashed with brine (10 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-46ccfc74bc994da8839fcf3e9d9b7216
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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