Triethylamine → 1-[(6-tert-Butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-4-[(6-chloronaphthalen-2-yl)sulfonyl]-2-ethoxycarbonylpiperazine

HRID 352851

Reaction equation

HRID 352851 reaction equation
[C:1]([O:5][C:6]([CH:8]1[NH:13][CH2:12][C:11]2[S:14][C:15]([C:17]([OH:19])=O)=[N:16][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[CH:28]=[C:27]([S:32]([N:35]1[CH2:40][CH2:39][NH:38][CH:37]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36]1)(=[O:34])=[O:33])[CH:26]=[CH:25]2.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[C:1]([O:5][C:6]([CH:8]1[NH:13][CH2:12][C:11]2[S:14][C:15]([C:17]([N:38]3[CH2:39][CH2:40][N:35]([S:32]([C:27]4[CH:26]=[CH:25][C:24]5[C:29](=[CH:30][CH:31]=[C:22]([Cl:21])[CH:23]=5)[CH:28]=4)(=[O:34])=[O:33])[CH2:36][CH:37]3[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[O:19])=[N:16][C:10]=2[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 227094496-Boc-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acidHCID 227100751-[(6-Chloronaphthalen-2-yl)sulfonyl]-3-ethoxycarbonylpiperazine hydrochloride

Product 1

HCID 227095171-[(6-tert-Butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-4-[(6-chloronaphthalen-2-yl)sulfonyl]-2-ethoxycarbonylpiperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (30 ml), 6-tert-butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid (WO94/21599) (742 mg), 1-[(6-chloronaphthalen-2-yl)sulfonyl]-3-ethoxycarbonylpiperazine hydrochloride (WO96/10022) (1.00 g) and benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP®) (1.50 g) were dissolved. Triethylamine (0.40 ml) was added to the resulting solution, followed by stirring overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the residue. The resulting mixture was washed with water and saturated aqueous NaCl solution and then, dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (hexane ethyl acetate=4:1), whereby the title compound (505 mg, 30%) was obtained.

Workup

  1. concentrationAfter the reaction mixture was concentrated under reduced pressure, ethyl acetate
  2. additionwas added to the residue
  3. washThe resulting mixture was washed with water and saturated aqueous NaCl solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe residue obtained
  6. distillationby distilling off the solvent under reduced pressure
  7. customwas purified by chromatography on a silica gel column (hexane ethyl acetate=4:1), whereby the title compound (505 mg, 30%)
  8. customwas obtained

Sources & evidence

ORD record
ord-93559d8da7be42c5ae2bb390dae84e41
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Linked notes

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