tert-Butyl piperazine-1-carboxylate → HCID 69937470, compound

HRID 2298642Notes

Reaction equation

HRID 2298642 reaction equation
[C:1]([O:5][C:6]([NH:8][N:9]=[CH:10][C:11]1[S:15][C:14]([CH3:16])=[C:13]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:30]=[CH:31][CH:32]=3)[O:25][CH2:26][C:27](O)=[O:28])[N:21]=2)[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].OC1C2N=NNC=2C=CC=1.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][N:9]=[CH:10][C:11]1[S:15][C:14]([CH3:16])=[C:13]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:30]=[CH:31][CH:32]=3)[O:25][CH2:26][C:27]([N:53]3[CH2:54][CH2:55][N:50]([C:48]([O:47][C:43]([CH3:46])([CH3:44])[CH3:45])=[O:49])[CH2:51][CH2:52]3)=[O:28])[N:21]=2)[CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53716194HCID 53716194, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 69937470HCID 69937470, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 40 mg (0.084 mmol) of 2-{3-[2-(5-{[(tert-butoxy)carbonylamino]iminomethyl}-2-methyl-3-thienyl)-1,3-thiazol-4-yl]phenoxy}acetic acid dissolved in dry dimethylformamide (5 mL) was treated with hydroxybenzotriazole (23 mg, 0.17 mmol), 32 mg (0.17 mmol) of N-tert-butoxycarbonyl-piperazine (Lancaster, Windham, N.H., USA), 65 mg (0.17 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) at room temperature for 20 h. The mixture was partitioned between dichloromethane (50 mL) and brine (50 mL). The aqueous layers were extracted twice with dichloromethane (50 mL) and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The solvents were removed in vacuo. Purification preparative thin layer chromatography eluting with dichloromethane:methanol 95/5 (v:v) gave tert-butyl 4-(2-{3-[2-(5-{[(tert-butoxy)carbonylamino]iminomethyl}-2-methyl-3-thienyl)-1,3-thiazol-4-yl]phenoxy}acetyl)piperazinecarboxylate (25 mg, 46%) as a white solid. 1H-NMR (DMSO-d6; 300 MHz) δ9.13 (br s, 2H), 8.50 (s, 1H), 8.20 (s, 1H), 7.63 (m, 2H), 7.39 (m, 1H), 6.95 (m, 1H), 4.93 (s, 2H), 3.47-3.34 (m, 8H), 2.82 (s, 3H), 1.45 (s, 9H), 1.42 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C31H39N5O6S2 642.3 (M+H), 542.3 ((M-BOC)+H), 442.3 ((M-2 BOC)+H), found 642.0, 542.2, 442.3.

Workup

  1. customThe mixture was partitioned between dichloromethane (50 mL) and brine (50 mL)
  2. extractionThe aqueous layers were extracted twice with dichloromethane (50 mL)
  3. washthe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvents were removed in vacuo
  6. customPurification preparative thin layer chromatography
  7. washeluting with dichloromethane

Sources & evidence

ORD record
ord-1875141db5aa4da0b1463f2269a3c517
Source dataset
uspto-grants-2002_12
Patent number
US06492403B1

Reaction notes

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