Triethylamine → HCID 178425140, compound

HRID 1501062Notes

Reaction equation

HRID 1501062 reaction equation
[O:1]([CH:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([OH:19])=O)=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.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>[OH:61][C:54]1[C:53]([CH2:52][NH:51][C:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[CH:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH2:10]3)=[O:19])=[C:58]([CH3:59])[CH:57]=[C:56]([CH3:60])[N:55]=1

Participants

6

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 89582819HCID 89582819, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425140HCID 178425140, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-phenoxy-2,3-dihydro-1H-indene-5-carboxylic acid (100 mg, 0.39 mmol) in dichloromethane (50 mL) were added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (190 mg, 0.5 mmol) and triethylamine (71 mg, 0.7 mmol). And then the mixture was stirred for 30 minutes. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (61 mg, 0.4 mmol) was added. The mixture was stirred at room temperature for 12 hours. The resultant mixture was washed with water (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by prep-TLC (silica gel, dichloromethane/methanol=20:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-1-phenoxy-2,3-dihydro-1H-indene-5-carboxamide (Compound I-45) (35 mg, 23%) as white solid. LRMS (M+H+) m/z: calcd 388.18. found 388. HPLC purity (214 nm): 99%. 1H NMR (300 MHz, d6-DMSO): δ 11.47 (s, 1H), 8.33 (s, 1H), 8.30 (s, 1H), 7.70 (d, J=7.8 Hz, 1H), 7.41-7.29 (m, 3H), 7.05-6.93 (m, 3H), 5.89-5.86 (m, 2H), 4.30 (d, J=4.8 Hz, 2H), 3.10-2.84 (m, 2H), 2.64-2.56 (m, 1H), 2.16 (s, 3H), 2.11 (s, 3H), 2.09-1.98 (m, 1H).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. washThe resultant mixture was washed with water (50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue
  7. customThe residue was purified by prep-TLC (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-5f93905e6d7841c998bf1b5d3528129a
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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