Triethylamine → 3-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)-1H-indol-5-yl 6-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoate

HRID 1422502Notes

Reaction equation

HRID 1422502 reaction equation
O[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1)=[O:3].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][C:54]([O:56][C:57]1[CH:58]=[C:59]2[C:63](=[CH:64][CH:65]=1)[NH:62][CH:61]=[C:60]2[CH2:66][CH2:67][NH:68][C:69]1[N:77]=[C:76]([C:78]2[C:79]3[CH:86]=[CH:85][CH:84]=[CH:83][C:80]=3[S:81][CH:82]=2)[N:75]=[C:74]2[C:70]=1[N:71]=[CH:72][N:73]2[CH:87]([CH3:89])[CH3:88])=[O:55]>CN(C=O)C>[O:14]=[C:13]1[NH:12][C@H:11]2[CH2:10][S:9][C@@H:8]([CH2:7][CH2:6][CH2:5][CH2:4][C:2]([NH:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][C:54]([O:56][C:57]3[CH:58]=[C:59]4[C:63](=[CH:64][CH:65]=3)[NH:62][CH:61]=[C:60]4[CH2:66][CH2:67][NH:68][C:69]3[N:77]=[C:76]([C:78]4[C:79]5[CH:86]=[CH:85][CH:84]=[CH:83][C:80]=5[S:81][CH:82]=4)[N:75]=[C:74]4[C:70]=3[N:71]=[CH:72][N:73]4[CH:87]([CH3:89])[CH3:88])=[O:55])=[O:3])[C@H:16]2[NH:15]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 171548BiotinHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594089403-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)-1H-indol-5-yl 6-aminohexanoate

Product 1

HCID 594089253-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)-1H-indol-5-yl 6-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (+)-biotin (35 mg, 0.14 mmol) and Et3N (36 mg, 0.35 mmol) in DMF (1 ml) was added HATU (90 mg, 0.24 mmol). The mixture was stirred for 10 min, and then was added to a solution of (3-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)-1H-indol-5-yl 6-aminohexanoate (b) (68 mg, 0.12 mmol) in DMF (1 ml). The reaction mixture was stirred for 16 hr at rt and then was concentrated. The residue was purified by reverse-phase HPLC (C18 column, eluting with MeOH—H2O 0.05% TFA) to afford the title compound as an off-white solid. Example 210 showed an EC50 value in the % CD34+ assay of 2.1 μM.

Workup

  1. stirringThe reaction mixture was stirred for 16 hr at rt
  2. concentrationwas concentrated
  3. customThe residue was purified by reverse-phase HPLC (C18 column, eluting with MeOH—H2O 0.05% TFA)

Sources & evidence

ORD record
ord-a79b2e103de8447e9fa506457624c31e
Source dataset
uspto-grants-2015_01
Patent number
US08927281B2

Reaction notes

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