Triethylamine → (6-{6-[5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoylamino}-hexyl)-carbamic Acid tert-Butyl Ester

HRID 1616995Notes

Reaction equation

HRID 1616995 reaction equation
O=C1CCC(=O)N1O[C:9](=[O:31])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:30])[CH2:17][CH2:18][CH2:19][CH2:20][CH:21]1[CH:28]2[CH:24]([NH:25][C:26](=[O:29])[NH:27]2)[CH2:23][S:22]1.C(N(CC)CC)C.[C:39]([O:43][C:44](=[O:53])[NH:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][NH2:52])([CH3:42])([CH3:41])[CH3:40]>CN(C=O)C>[C:39]([O:43][C:44](=[O:53])[NH:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][NH:52][C:9](=[O:31])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:30])[CH2:17][CH2:18][CH2:19][CH2:20][CH:21]1[CH:28]2[CH:24]([NH:25][C:26](=[O:29])[NH:27]2)[CH2:23][S:22]1)([CH3:42])([CH3:40])[CH3:41]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2733170N-BOC-1,6-diaminohexaneHCID 5063989Biotin-X-NHS

Product 1

HCID 86762490(6-{6-[5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoylamino}-hexyl)-carbamic Acid tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

6-[5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoic acid 2,5-dioxo-pyrrolidin-1-yl ester (4; 0.39 g, 0.86 mmol) was completely dissolved in DMF (15 mL) with gentle warming. After cooling the solution to room temperature without reprecipitation, it was mixed with triethylamine (Et3N; 0.52 g, 5.15 mmol) followed by the addition of 5 (0.25 g, 1.14 mmol) in DMF (3 mL) dropwise while stirring. After overnight reaction at room temperature, the mixture was filtered, evaporated in vacuo, and loaded to a silica column for further purification. The products were separated by eluting with mobile phases of 5-20% MeOH in DCM to afford 6 (0.45 g; 93.8%) as a yellowish solid. 1H NMR (400 MHz) (CD3OD) δ: 4.53 (t, 1H, CHN), 4.34 (t, 1H, CHN), 3.25 (dd, 1H, CHS), 3.20 (t, 2H, CH2NH), 3.08 (t, 2H, CH2NH), 2.96 (d, 1H, CHHS), 2.73 (d, 1H, CHHS), 2.22 (t, 4H, CH2CO), 1.38-1.80 (m, 29H). 13C NMR (100.67 MHz) (DMSO) δ: 176.02, 175.97, 166.05, 158.50, 79.50, 63.39, 61.63, 57.01, 41.24, 41.04, 40.24, 36.99, 36.82, 30.90, 30.35, 30.13, 29.78, 29.49, 28.80, 27.56, 26.92, 26.74. HRMS (ESI) calculated for C27H49N5O5S, [M+Na]+ 578.3352 (calcd.), 578.3349 (found).

Workup

  1. customwithout reprecipitation, it
  2. customAfter overnight reaction at room temperature
  3. filtrationthe mixture was filtered
  4. customevaporated in vacuo
  5. customloaded to a silica column for further purification
  6. customThe products were separated
  7. washby eluting with mobile phases of 5-20% MeOH in DCM
  8. customto afford 6 (0.45 g; 93.8%) as a yellowish solid

Sources & evidence

ORD record
ord-e41a73a1ff92496499aa4a70c2f732cd
Source dataset
uspto-grants-2014_07
Patent number
US08765934B2

Reaction notes

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