Triethylamine → HCID 178425187, compound

HRID 1500961Notes

Reaction equation

HRID 1500961 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([C@@H:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:51][CH2:52][C:53]1[C:54]([OH:61])=[N:55][C:56]([CH3:60])=[CH:57][C:58]=1[CH3:59]>ClCCl.O>[OH:61][C:54]1[C:53]([CH2:52][NH:51][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][C:9]([C@@H:11]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:12])=[CH:10][C:2]=2[CH3:1])=[C:58]([CH3:59])[CH:57]=[C:56]([CH3:60])[N:55]=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 89580965HCID 89580965, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425187HCID 178425187, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-methyl-4-(1-phenoxyethyl)benzoic acid (5.3 g, 19.5 mmol) in dichloromethane (100 mL) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (11.1 g, 29.3 mmol) and triethylamine (8.6 mL, 62.2 mmol). The mixture was stirred at room temperature for 30 minutes. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (3.15 g, 21 mmol) was added and the mixture was stirred at room temperature for 12 hours. The mixture was poured into water (100 mL) and extracted with dichloromethane (50 mL*2). The combined organic phase was separated, dried by sodium sulphate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, methanol/dichloromethane=1:10) to give (S)—N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-methyl-4-(1-phenoxyethyl)benzamide (Compound I-55) as a white solid (4.5 g, 59%). LRMS (M+H+) m/z: calcd 390.19. found 390. HPLC purity (214 nm): 100%. 1H NMR (300 MHz, CD3OD): δ 7.28-7.22 (m, 3H), 7.12-7.09 (m, 2H), 6.83-6.79 (m, 3H), 6.10 (s, 1H), 5.36-5.34 (m, 1H), 4.44 (s, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.23 (s, 3H), 1.57 (d, J=6.6 Hz, 3H).

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hours
  2. extractionextracted with dichloromethane (50 mL*2)
  3. customThe combined organic phase was separated
  4. dry with materialdried by sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue
  8. customThe residue was purified by column chromatography (silica gel, methanol/dichloromethane=1:10)

Sources & evidence

ORD record
ord-c326a71e0c35424aa952dd8776e983ce
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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