Triethylamine → HCID 86585855, compound

HRID 1783224Notes

Reaction equation

HRID 1783224 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])=[O:13])[CH:11]=1)[C:6]([OH:8])=O)#[N:2].[NH2:21][C@@H:22]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@H:23]([OH:42])[CH2:24][N:25]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=1)[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29].C(OP(C#N)(=O)OCC)C.C(N(CC)CC)C>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])=[O:13])[CH:11]=1)[C:6]([NH:21][C@@H:22]([CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C@H:23]([OH:42])[CH2:24][N:25]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=1)[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:8])#[N:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 225936383-Cyano-5-[(dipropylamino)carbonyl]Benzoic AcidHCID 58759815HCID 58759815, compound

Product 1

HCID 86585855HCID 86585855, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-cyano-5-[(dipropylamino)carbonyl]benzoic acid (IX/XXXII, PREPARATION 7, 0.086 g, 0.314 mmol) and tert-butyl (2R,3S)-3-amino-2-hydroxy-4-phenylbutyl(3-methoxybenzyl)carbamate (XXXV, EXAMPLE 584, 0.126 g, 0.314 mmol) in dichloromethane (0.3 mL) is added diethylcyanophosphonate (0.062 g, 0.330 mmol) and triethylamine (0.032 g, 0.316 mmol). The mixture is stirred at 20-25 degrees for 65 hours and then partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase is separated and dried over sodium sulfate and concentrated. The residue is chromatographed (silica gel, 20 mL; methanol/dichloromethane, 5/95) to give several mixed fractions, which are combined and rechromatographed (silica gel; acetone/hexane, 20/80) to give the title compound, MS (ESI+) for C38H48N4O6 m/z 657.6 (M+H)+=657.6; (M+Na)=679.5 and (M-C4H9O2)=557.5.

Workup

  1. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  2. customThe organic phase is separated
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is chromatographed (silica gel, 20 mL; methanol/dichloromethane, 5/95)
  6. customto give several
  7. additionmixed fractions, which
  8. customrechromatographed (silica gel; acetone/hexane, 20/80)

Sources & evidence

ORD record
ord-3d482f4816a14eb0bd2a19510aac6c7a
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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