Tridecanoic acid → HCID 10295891, compound

To a 500 mg-batch of ArgoGel MB-OH (from Argonaut; loading 0.4 mmol/g, 0.2 mmol) was added a solution of 163 mg (1 mmol, 5 eq.) carbonyldiimidazole and 171 μl (1 mmol, 5 eq.) DIEA in 5 ml of dry THF, and the resulting mixture was allowed to react for 7 h at room temperature under gentle shaking. After this time, the resin was washed with THF (2×), DCM (2×), DMF (1×) and then directly used for the following step. The resin was allowed to react for 15 h at room temperature with a solution of 230 μl (2 mmol, 10 eq.) 1,6-hexanediamine (see compound VIIa in Scheme 2) and 342 μl (2 mmol, 10 eq.) DIEA in 5 ml DMF. After this time, the resin batches were washed with DMF (3×), DCM (1×), THF (2×), DCM (3×), and Et2O (2×) and dried in vacuo. To the resulting resin batch was added a solution of 211 mg (0.6 mmol, 3 eq.) Fmoc-D-pipecolic acid (see compound IIa in Scheme 2), 228 mg (0.6 mmol, 3 eq.) HATU, and 206 μl (1.2 mmol, 6 eq.) DIEA in 3 ml anhydr. DMF. After a reaction time of 8 h at ambient temperature, the resin was washed with DMF (5×), DCM (5×), DMF (5×), DCM (3×), Et2O (2×), and dried in vacuo. The resin was now treated with 4ml of a solution of 20% (v/v) piperidine in DMF for 20 min at room temperature, then washed with DMF (5×), DCM (5×), DMF (5×). To the resulting resin was added a solution of 129 mg (0.6 mmol, 3 eq.) tridecanoic acid (see compound V in Scheme 2), 228 mg (0.6 mmol, 3 eq.) HATU, and 206 μl (1.2 mmol, 6 eq.) DIEA in 3 ml anhydr. DMF. After a reaction time of 8h at room temperature, the reaction was worked up by washing with DMF (5×), DCM (5×), DMF (5×), DCM (3×), Et2O (2×), and the resin batches were dried in vacuo at r.t. O/N. The resin was treated with a solution of 20% (v/v) TFA in DCM for 10 min at room temperature, to release the title compound from the resin in 60% overall yield.

1. customto react for 7 h at room temperature under gentle shaking
2. washAfter this time, the resin was washed with THF (2×), DCM (2×), DMF (1×)
3. washAfter this time, the resin batches were washed with DMF (3×), DCM (1×), THF (2×), DCM (3×), and Et2O (2×)
4. customdried in vacuo
5. washAfter a reaction time of 8 h at ambient temperature, the resin was washed with DMF (5×), DCM (5×), DMF (5×), DCM (3×), Et2O (2×)
6. customdried in vacuo
7. additionThe resin was now treated with 4ml of a solution of 20% (v/v) piperidine in DMF for 20 min at room temperature
8. washwashed with DMF (5×), DCM (5×), DMF (5×)
9. customat room temperature
10. washby washing with DMF (5×), DCM (5×), DMF (5×), DCM (3×), Et2O (2×)
11. customthe resin batches were dried in vacuo at r.t
12. additionThe resin was treated with a solution of 20% (v/v) TFA in DCM for 10 min at room temperature

ORD record

ord-ba0cf038119242879302f67efba18b38

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06770656B2