Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 1,1-Dimethylethyl 4-[5-[[methyl[(1R)-1-phenylethyl]amino]carbonyl]-2-thiazolyl]-1-piperazinecarboxylate

HRID 2043721Notes

Reaction equation

HRID 2043721 reaction equation
[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:5]=1)([OH:3])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CC1C=CC(C)=CC=1CC(N1CCC(C2SC=C([C:68]([N:70](C)[C@@H:71]([C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)[CH2:72]C)=O)N=2)CC1)=O>C(#N)C>[CH3:68][N:70]([C@@H:71]([C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)[CH3:72])[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:5]=1)=[O:3]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672940122-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}-1,3-thiazole-5-carboxylic acid2×HCID 674615172-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1-phenylpropyl]-4-thiazolecarboxamide

Product 1

HCID 674613901,1-Dimethylethyl 4-[5-[[methyl[(1R)-1-phenylethyl]amino]carbonyl]-2-thiazolyl]-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-(1,1-Dimethylethyl) 4-(5-carboxy-2-thiazolyl)-1-piperazinecarboxylate (i.e. the product of Example 4, Step B) (1.0 g, 3.2 mmol) was suspended in 10 mL of dry acetonitrile and treated with triethylanaine (892 μL, 6.4 mmol) to give a homogeneous solution. To this was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.33 g, 3.5 mmol) followed by (α,R)—N,α-dimethylbenzenemethanamine (i.e. the product of Example 1, Step C) (200 μL, 1.38 mmol). The reaction mixture was stirred at ambient temperature for 3 days, concentrated under reduced pressure, diluted with ethyl acetate, washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate and concentrated under reduced pressure to give 1.38 g of an orange foam. Purification by silica gel chromatography using an ethyl acetate/hexanes gradient from 1:9 to 100:0 gave 0.78 g of the title compound as a yellow solid.

Workup

  1. additiontreated with triethylanaine (892 μL, 6.4 mmol)
  2. customto give a homogeneous solution
  3. concentrationconcentrated under reduced pressure
  4. additiondiluted with ethyl acetate
  5. washwashed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2d2a870a6bba404daa82c3c6640610eb
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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