Diisopropylethylamine → HCID 10145777, compound

HRID 14308Notes

Reaction equation

HRID 14308 reaction equation
[CH3:1][N:2]([CH2:20][CH2:21][CH3:22])[C:3]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([C:15]2[S:16][CH:17]=[CH:18][N:19]=2)[CH:14]=1)[C:8]([O:10]C)=O)=[O:4].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:58][C@@H:59]([CH2:73][C:74]1[CH:79]=[C:78]([F:80])[CH:77]=[C:76]([F:81])[CH:75]=1)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=1>O1CCCC1.CO.O.O.[OH-].[Li+].C(OCC)(=O)C>[F:80][C:78]1[CH:79]=[C:74]([CH:75]=[C:76]([F:81])[CH:77]=1)[CH2:73][C@H:59]([NH:58][C:8](=[O:10])[C:7]1[CH:12]=[C:13]([C:15]2[S:16][CH:17]=[CH:18][N:19]=2)[CH:14]=[C:5]([C:3]([N:2]([CH3:1])[CH2:20][CH2:21][CH3:22])=[O:4])[CH:6]=1)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21086191Methyl 3-{[methyl(propyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoateHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Product 1

HCID 10145777HCID 10145777, compound

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 168937Lithium hydroxide, monohydrateSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Methyl 3-{[methyl(propyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoate (390 mg, 1.22 mmol) is dissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate is added (103 mg, 2.4 mmol), and the reaction stirred 2 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (355 μL, 2.0 mmol), HATU (230 mg, 0.61 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method of EXAMPLE SP-272 (206 mg, 0.51 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9% methanol/methylene chloride) provides the title compound. ESI MS m/z 621.3 [M+H]+.

Workup

  1. additionis added (103 mg, 2.4 mmol)
  2. concentrationThe solution is concentrated under reduced pressure
  3. dissolutionThe residue is redissolved in DMF (5 mL)
  4. additionare added
  5. stirringThe reaction stirred at room temperature 16 h
  6. washwashed with water, saturated sodium bicarbonate, saturated sodium chloride
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, 9% methanol/methylene chloride)

Sources & evidence

ORD record
ord-a4d61051d3b6425082e5647c85c65c7b
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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