Triethylamine → 2-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]annulen-2-yl)oxy]ethoxy}ethyl {2-[2-(2-{[-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]amino}ethoxy) ethoxy]ethyl}carbamate

HRID 46014Notes

Reaction equation

HRID 46014 reaction equation
C(=O)(OC1C=CC=C([N+]([O-])=O)C=1)OCC[O:5][CH2:6][CH2:7][O:8][C:9]1[CH:29]=[CH:28][C:12]2[C:13]#[C:14][C:15]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:19][C:16]=3[CH2:17][CH2:18][C:11]=2[CH:10]=1.CCN(CC)CC.[C:48]([NH:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60][O:61][CH2:62][CH2:63][NH:64][C:65](=[O:79])[CH2:66][CH2:67][CH2:68][CH2:69][C@H:70]1[C@@H:78]2[C@@H:73]([NH:74][C:75]([NH:77]2)=[O:76])[CH2:72][S:71]1)([O:50][C:51]([CH3:54])(C)C)=[O:49]>CN(C=O)C>[O:76]=[C:75]1[NH:74][CH:73]2[CH2:72][S:71][CH:70]([CH2:69][CH2:68][CH2:67][CH2:66][C:65]([NH:64][CH2:63][CH2:62][O:61][CH2:60][CH2:59][O:58][CH2:57][CH2:56][NH:55][C:48](=[O:49])[O:50][CH2:51][CH2:54][O:5][CH2:6][CH2:7][O:8][C:9]3[CH:29]=[CH:28][C:12]4[C:13]#[C:14][C:15]5[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:19][C:16]=5[CH2:17][CH2:18][C:11]=4[CH:10]=3)=[O:79])[CH:78]2[NH:77]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10600603Biotin-PEG2-NH-BocHCID 871480662-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]annulen-2-yl)oxy]ethoxy}ethyl 3-nitrophenyl carbonate

Product 1

HCID 750461652-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]annulen-2-yl)oxy]ethoxy}ethyl {2-[2-(2-{[-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]amino}ethoxy) ethoxy]ethyl}carbamateYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of carbonate 16 (0.15 g, 0.28 mmol) in DMF (approximately 2 mL) was added to a solution of Et3N (0.5 g, 4.95 mmol) and N-Boc-N′-biotinyl-3,6-dioxaoctane-1,8-diamine (Ning et al., Angew. Chem. Int. Ed. 2008, 47:2253-2255) (0.01 g, 0.28 mmol) in DMF (10 mL) at room temperature. The reaction mixture was stirred overnight at room temperature, most solvent was evaporated under reduced pressure, and the residue was separated by chromatography on (CH2Cl2:MeOH 30:1) to provide 0.164 g (0.21 mmol, 75%) of 6b. 1H NMR δ 7.19 (d, J=8.4 Hz, 2H), 6.88 (dd, J=9.5, 2.5 Hz, 2H), 6.76 (td, J=8.2, 2.5, 2H), 6.74-6.65 (m, 1H), 6.54 (s, b, 1H), 5.74 (s, b, 1H), 5.60 (s, b 1H), 4.49-4.43 (m, 1H), 4.29-4.22 (m, 3H), 4.16-4.10 (m, 2H), 3.97 (t, J=6.5, 2H), 3.87-3.81 (m, 2H), 3.76 (m, 2H), 3.59-3.48 (m, 7H), 3.42 (m, 2H), 3.37-3.12 (m, 2H), 3.21-3.09 (m, 4H), 2.86 (dd, J=12.6, 4.7 Hz, 1H), 2.72 (d, J=12.7, 1H), 2.42 (d, J=10.9, 2H), 2.21 (t, J=7.4, 2H), 1.81-1.56 (m, 5H), 1.48 (sex, J=7.4 Hz, 2H), 1.44-1.36 (m, 2H), 1.32 (t, J=7.4 Hz, 1H), 0.98 (t, J=7.4, 3H); 13C NMR δ 173.4, 164.1, 158.7, 158.1, 156.5, 154.8, 126.66, 126.63, 116.80, 116.72, 116.59, 115.8, 111.91, 111.83, 110.67, 110.14, 70.09, 70.04, 69.95, 69.90, 69.80, 69.54, 67.78, 67.52, 63.88, 61.80, 60.2, 55.6, 45.6, 40.8, 40.5, 39.1, 36.63, 36.61, 35.9, 31.3, 28.22, 28.08, 25.6, 19.2, 13.8, 8.5.

Workup

  1. custommost solvent was evaporated under reduced pressure
  2. customthe residue was separated by chromatography on (CH2Cl2:MeOH 30:1)

Sources & evidence

ORD record
ord-d5983fd14b6c4c6d9834e33d7a0563cf
Source dataset
uspto-grants-2013_09
Patent number
US08541625B2

Reaction notes

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