Triethylamine → n-[1-Benzyloxycarbonyl-2-(1h-indol-3-yl)-ethyl]-3-{[benzyloxy-(4-phenyl-butyl)-phosphinoyl]-amino}-succinamic acid benzyl ester

HRID 902956Notes

Reaction equation

HRID 902956 reaction equation
[CH2:1]([O:8][PH:9]([CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([CH:25]([Si](C)(C)C)[C:26](N)=O)(C)C.[NH2:33][C@H:34]([C:46]([NH:48][C@H:49]([C:68]([OH:70])=[O:69])[CH2:50][C:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[N:53](OCC2C=CC=CC=2)[CH:52]=1)=[O:47])[CH2:35][C:36](=[O:45])[O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CCN([CH2:76][CH3:77])CC.[C:78](Cl)(Cl)(Cl)Cl.[CH3:83][C:84]#N>>[CH2:38]([O:37][C:36](=[O:45])[CH2:35][CH:34]([NH:33][P:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:10])[C:46]([NH:48][CH:49]([C:68]([O:70][CH2:78][C:26]1[CH:25]=[CH:77][CH:76]=[CH:84][CH:83]=1)=[O:69])[CH2:50][C:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[NH:53][CH:52]=1)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 5

HCID 8471TriethylamineHCID 11708267BistrimethylsilylacetamidHCID 18669661Acetonitrile tetrachloromethaneHCID 131725939H-Asp(OBn)-Trp(OBn)HCID 178527035HCID 178527035, compound

Product 1

HCID 69212717n-[1-Benzyloxycarbonyl-2-(1h-indol-3-yl)-ethyl]-3-{[benzyloxy-(4-phenyl-butyl)-phosphinoyl]-amino}-succinamic acid benzyl esterYield 44%

Procedure

To a stirred solution of the phosphinate of Example 81 (144 mg, 0.50 mmol) in dry degassed acetonitrile (1.5 mL), was added bis-(trimethylsilyl)acetamide (73 μL, 0.30 mmol) followed immediately by the addition of a solution of H-Asp(OBn)-Trp(OBn), [Example 83 (322 mg, 0.60 mmol)] and Et3N (209 μL, 1.5 mmol) in CCl4/CH3CN (3:1, 2 mL). The reaction mixture was stirred at room temperature for 14 h and then concentrated in vacuum. Purification by flash chromatography using a gradient of EtOAc in hexane (50% to 100%) provided the title compound (0.175 g, 44%) as a white residue: Rf l(100% EtOAc)=0.5; 1H NMR (CDCl3) δ 8.5 (d, 1H), 7.6 (d, 1H), 7.5-6.9 (m, 25), 5.2-4.9 (m, 6H), 4.83 (dd, 1H), 4.63 (dd, 1H), 4.22 (m, 1H), 3.91(d, 1H), 3.36 (dt, 1H), 3.28 (dt,1H), 3.01 (dd, 1H), 2.65 (dt, 1H), 2.50 (m, 2H), 1.71-1.25 (m, 6H); 31P NMR (CDCl3) δ 35.6.

Workup

  1. customdegassed acetonitrile (1.5 mL)
  2. concentrationconcentrated in vacuum
  3. customPurification by flash chromatography

Sources & evidence

ORD record
ord-b9c4e48f4bfa4eae8ee5aa82681774b7
Source dataset
uspto-grants-2008_04
Patent number
US07365091B2

Reaction notes

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