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

HRID 1616996Notes

Reaction equation

HRID 1616996 reaction equation
O=C1CCC(=O)N1O[C:9](=[O:19])[CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[NH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:50])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:34][C:35](=[O:49])[CH2:36][CH2:37][CH2:38][CH2:39][CH:40]1[CH:47]2[CH:43]([NH:44][C:45](=[O:48])[NH:46]2)[CH2:42][S:41]1.CCN(CC)CC>CN(C=O)C>[C:15]([O:14][C:12](=[O:13])[NH:11][CH2:10][C:9](=[O:19])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:50])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:34][C:35](=[O:49])[CH2:36][CH2:37][CH2:38][CH2:39][CH:40]1[CH:47]2[CH:43]([NH:44][C:45](=[O:48])[NH:46]2)[CH2:42][S:41]1)([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76926N-(tert-Butyloxycarbonyl)glycine N-hydroxysuccinimide esterHCID 86667755HCID 86667755, compound

Product 1

HCID 86667754[(6-{6-[5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoylamino}-hexylcarbamoyl)-methyl]-carbamic Acid tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Tert-Butoxycarbonylamino-acetic acid 2,5-dioxo-pyrrolidin-1-yl ester (8b; 0.18 g, 0.69 mmol) dissolved in DMF (5 mL) was added slowly to a DMF solution (3 mL) containing 6-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-hexanoic acid (6-amino-hexyl)-amide (7; 0.16 g, 0.27 mmol) and Et3N (0.1 mL, 0.72 mmol) while stirring at room temperature. The reaction was stopped after 3 h by evaporating DMF in vacuo, and the remaining residue was redissolved in a limited volume of a DCM/MeOH (19:1) solution and loaded to a preequilibrated silica column. The products were separated by eluting with mobile phases of 1-6.67% MeOH in DCM to afford 9 (0.10 g; 62.2%) as a yellow solid. 1H NMR (400 MHz) (CD3OD) δ: 4.30 dd, 1H, CHN), 4.15 (dd, 1H, CHN), 3.94 (d, 2H, CH2CO), 3.32 (quin, 4H, CH2NH), 2.99 (q, 2H, CH2N), 2.92 (d, 1H, CHHS), 2.75 (d, 1H, CHHS), 2.20 (t, 4H, CH2CO), 1.44-1.88 (m, 29H). 13C NMR (100.67 MHz) (CD3OD) δ: 175.9 (CO), 63.7 (CHN), 61.6 (CHN), 56.9 (CHS), 49.0 (CH2N), 41.0 (CH2CO), 40.2 (CH2N), 36.9 (CH2S), 30.1 (CH2CO), 28.6 (CH3CO), 26.7 (CH2CH2). HRMS (ESI) calculated for C29H52N6O6S, [M+Na]+ 635.3567 (calcd.), 635.3564 (found).

Workup

  1. customby evaporating DMF in vacuo
  2. dissolutionthe remaining residue was redissolved in a limited volume of a DCM/MeOH (19:1) solution
  3. customThe products were separated
  4. washby eluting with mobile phases of 1-6.67% MeOH in DCM
  5. customto afford 9 (0.10 g; 62.2%) as a yellow solid

Sources & evidence

ORD record
ord-97db8dae52d44a07a31b66021d72d7d1
Source dataset
uspto-grants-2014_07
Patent number
US08765934B2

Reaction notes

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