Diisopropylethylamine → HCID 24900572, compound

HRID 709593Notes

Reaction equation

HRID 709593 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][CH2:9][C:10]([OH:12])=O)=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:37][C:38]1[CH:39]=[CH:40][CH:41]=[C:42]2[C:47]=1[NH:46][CH2:45][CH2:44][CH2:43]2.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][CH2:9][C:10]([N:46]2[C:47]3[C:42](=[CH:41][CH:40]=[CH:39][C:38]=3[CH3:37])[CH2:43][CH2:44][CH2:45]2)=[O:12])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27741668-Methyl-1,2,3,4-tetrahydroquinolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 24694245HCID 24694245, compound

Product 1

HCID 24900572HCID 24900572, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (5-chloro-pyridin-2-ylsulfanyl)-acetic acid (15, 0.27 g, 1.3 mmol) in dry CH2Cl2 (10 mL) and DMF (2 mL) at 0° C. was added HATU (0.5 g, 1.3 mmol) and reaction mixture was stirred for 30 min at ambient temperature. Then the reaction mixture was cooled to 0° C. and neat 8-methyl-1,2,3,4-tetrahydroquinolin (0.20 g, 1.3 mmol) was added via syringe followed by addition of DIPEA, (0.69 mL, 3.9 mmol). The reaction mixture was allowed to warm to room temperature over 18 h. The reaction mixture was diluted with 50 mL of CH2Cl2, washed with H2O, 10% citric acid, NaHCO3 (saturated), brine, dried over Na2SO4 and concentrated. The crude was purified by column chromatography (hexanes/EtOAc) to give 90 mg of the target 16 as a white solid in 20% yield. MS (APCI) m/z: 333.1 (100%, [M+H]+, 186.0 (20%, [M−147+H]+; HPLC purity: 100%; Anal. Calcd. for C17H17ClN2OS: C, 61.34; H, 5.15; N, 8.42; Cl, 10.65; S, 9.63. Found: C, 61.33; H, 5.06; N, 8.36; Cl. 10.67; S, 9.56.

Workup

  1. temperatureThen the reaction mixture was cooled to 0° C.
  2. temperatureto warm to room temperature over 18 h
  3. washwashed with H2O, 10% citric acid, NaHCO3 (saturated), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude was purified by column chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-4c5491ff899f46048b528f6a1f0e8ea5
Source dataset
uspto-grants-2015_11
Patent number
US09181219B2

Reaction notes

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