Methanol → HCID 59362854, compound

HRID 1625460Notes

Reaction equation

HRID 1625460 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:24]=[C:25]([C:27]3[C:35]4[C:30](=[N:31][CH:32]=[CH:33][CH:34]=4)[N:29](S(C4C=CC=CC=4)(=O)=O)[CH:28]=3)[CH:26]=2)[O:19][CH2:20][C:21]([OH:23])=O)=[O:13])[C:7]1=[O:45].[Cl-].[NH4+].C[N:53](C)C=O.C(N(CC)C(C)C)(C)C.CO.C(=O)([O-])[O-].[K+].[K+]>O.CCOC(C)=O>[NH2:53][C:21](=[O:23])[CH2:20][O:19][C:18]1[CH:17]=[C:16]([CH:26]=[C:25]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[CH:33][CH:34]=3)[NH:29][CH:28]=2)[CH:24]=1)[CH2:15][NH:14][C:12]([C:8]1[C:7](=[O:45])[N:6]([CH2:5][C:4]2[CH:46]=[CH:47][C:48]([F:49])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][CH:9]=1)=[O:13]

Participants

9

Reactant 6

HCID 887MethanolHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 59362455HCID 59362455, compound

Product 1

HCID 59362854HCID 59362854, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mix of 2-(3-((1-(3,4-difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)methyl)-5-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)phenoxy)acetic acid (50 mg, 0.00007 mol;), Ammonium chloride (20 mg, 0.0004 mol;), and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl) pyridin Hexafluorophosphate (0.06 g, 0.0001 mol;) in N,N-Dimethylformamide (5 mL, 0.06 mol;) N,N-Diisopropylethylamine (0.06 mL, 0.0004 mol;) was stirred for overnight and LC-MS showed complete amide formation (1.71 min, ES+/684.37). Worked up with EtOAc and water. Dried over MgSO4 and concentrated. The residue was then dissolved in Methanol (10 mL, 0.2 mol;) and added Potassium carbonate (50 mg, 0.0004 mol;) and heated to reflux for 1 h. LC-MS showed the formation of the des-PhSO2 product C (1.24 min, ES+/544.53). Evaporated off the solvents and dissolved in DMSO and water and purified on Gilson HPLC to give the desired product (15 mg, 40%) MS (ES+) m/z 544.53 4 (M+1). 1H NMR (DMSO, 400 MHz): δ 8.41 (dd, 1H), 8.29 (d, 1H), 8.27 (dd, 1H), 8.24 (dd, 1H), 7.88 (s, 1H), 7.45-7.35 (m, 2H), 7.31 (s, 2H), 7.18 (m, 2H), 7.11 (dd, 1H), 6.83 (s, 1H), 6.60 (t, 1H), 5.22 (s, 2H), 4.55 (s, 2H), 4.49 (s, 2H),

Workup

  1. dry with materialDried over MgSO4
  2. concentrationconcentrated
  3. temperatureheated
  4. temperatureto reflux for 1 h
  5. customthe formation of the des-PhSO2 product C (1.24 min, ES+/544.53)
  6. customEvaporated off the solvents
  7. dissolutiondissolved in DMSO
  8. customwater and purified on Gilson HPLC

Sources & evidence

ORD record
ord-e62370ad5631490daeffa1ca94c34afa
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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