Triethylamine → HCID 178454575, compound

HRID 707419Notes

Reaction equation

HRID 707419 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@@H:13]([NH2:15])[CH2:12]1.[Cl:16][C:17]1[C:18]([C:23]([CH3:28])([CH3:27])[C:24](O)=[O:25])=[N:19][CH:20]=[CH:21][N:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl.O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@@H:11]1[CH2:12][C@H:13]([NH:15][C:24](=[O:25])[C:23]([C:18]2[C:17]([Cl:16])=[N:22][CH:21]=[CH:20][N:19]=2)([CH3:28])[CH3:27])[CH2:14]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866941182-(3-Chloropyrazin-2-yl)-2-methylpropanoic acid2×HCID 178511737HCID 178511737, compound2×

Product 1

HCID 178454575HCID 178454575, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a round bottomed flask was added cis-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine (Intermediate 32, 0.3010 g, 1.030 mmol), 2-(3-chloropyrazin-2-yl)-2-methylpropanoic acid (Intermediate 29, 0.248 g, 1.236 mmol), HATU (0.509 g, 1.339 mmol, GenScript Corp), and triethylamine (0.573 ml, 4.12 mmol, Sigma-Aldrich Chemical Company, Inc.) in DCM (2.060 ml) to stir at room temperature for 4 hours. The reaction mixture was diluted with water and extracted with CH2Cl2. The organic extract was washed with water, saturated NaHCO3, saturated NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product (592.4 mg) was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide the title compound (0.3181 g, 0.791 mmol, 77% yield). LCMS showed product peak at 1.536 min (m+1=401.9). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52 (s, 4 H) 1.88-2.03 (m, 1 H) 2.60-2.69 (m, 1 H) 3.87-4.03 (m, 1 H) 6.97-7.07 (m, 1 H) 7.18-7.26 (m, 1 H) 7.39 (d, J=7.43 Hz, 1 H) 7.63-7.71 (m, 1 H) 7.76 (d, J=6.65 Hz, 1 H) 8.27 (d, J=6.26 Hz, 1 H) 8.45 (d, J=2.54 Hz, 1 H) 8.68 (d, J=2.54 Hz, 1 H)

Workup

  1. extractionextracted with CH2Cl2
  2. extractionThe organic extract
  3. washwas washed with water, saturated NaHCO3, saturated NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
  8. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-1c1ee4699eed406497b3cc572d0ac4fa
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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