Benzylamine → HCID 11166421, compound

HRID 1866491Notes

Reaction equation

HRID 1866491 reaction equation
[OH:1][C@H:2]([C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH2:24][OH:25])[CH:18]=1)[CH2:3][NH:4][C@H:5]([CH3:16])[CH2:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=O.C(N(CC)CC)C.[CH2:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[NH3:4].[CH2:33]([NH:40][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][CH:15]=[C:7]([CH2:6][C@H:5]([NH:4][CH2:3][C@H:2]([OH:1])[C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH2:24][OH:25])[CH:18]=2)[CH3:16])[CH:8]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 57978199HCID 57978199, compound

Product 2

HCID 222AmmoniaHCID 11166421HCID 11166421, compoundYield 146.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-[(2R)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)propyl]benzoic acid (Preparation 59) (116 mg, 0.22 mmol) in DMF (2 ml) was added triethylamine (62 μl, 0.45 mmol), benzylamine (29 μl, 0.27 mmol), HOBt (33 mg, 0.25 mmol) and WSCDl (47 mg, 0.25 mmol) and the resulting solution stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue partitioned between saturated aqueous sodium hydrogen carbonate solution (5 ml) and dichloromethane/methanol (95/5) (10 ml). The aqueous layer was separated and extracted with further dichloromethane/methanol (95/5) (4×10 ml). The combined organic layers were dried (sodium sulfate), filtered and evaporated in vacuo. The resulting oil was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (90:10:1, by volume) to give the title compound as a white foam (70 mg). 1H NMR (400 MHz, CD3OD): δ=7.70-7.68 (1H, d), 7.66 (1H, s), 7.38-7.29 (6H, m), 7.26-7.21 (1H, m), 7.21 (1H, s), 7.03-7.01 (1H, d), 6.69-6.67 (1H, d), 4.64-4.61 (1H, m), 4.61 (2H, s), 4.58 (2H, s), 3.05-2.98 (1H, m), 2.92-2.86 (1H, dd), 2.84-2.79 (1H, dd), 2.75-2.71 (1H, dd), 2.68-2.63 (1H, dd), 1.10-1.08 (3H, d) ppm. LRMS (electrospray): m/z [M+H]+ 435, [M+Na]+ 457, [M−H]− 433. CHN analysis: found C, 69.79; H, 6.96; N, 6.37; C26H30N2O4+0.7H2O requires C, 69.84; H, 7.08; N, 6.26.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between saturated aqueous sodium hydrogen carbonate solution (5 ml) and dichloromethane/methanol (95/5) (10 ml)
  3. customThe aqueous layer was separated
  4. extractionextracted with further dichloromethane/methanol (95/5) (4×10 ml)
  5. dry with materialThe combined organic layers were dried (sodium sulfate)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resulting oil was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-333f834d49df4bf0be956cf468a58c19
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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