Sodium Hydroxide → 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidine-4-carboxylic acid

HRID 634213Notes

Reaction equation

[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]5[O:20][C:21]([NH:24][CH:25]([CH3:27])[CH3:26])=[N:22][N:23]=5)[CH:17]=4)[N:12](S(C4C=CC(C)=CC=4)(=O)=O)[CH:11]=3)[N:7]=[C:6]([C:38]([O:40]C)=[O:39])[CH:5]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>O1CCOCC1>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]5[O:20][C:21]([NH:24][CH:25]([CH3:27])[CH3:26])=[N:22][N:23]=5)[CH:17]=4)[NH:12][CH:11]=3)[N:7]=[C:6]([C:38]([OH:40])=[O:39])[CH:5]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 100 °C

Procedure

In a 5 mL microwave tube methyl 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxylate (16 mg, 0.028 mmol) was treated with dioxane (1 mL) and 1N NaOH (0.5 mL) and heated in the microwave at 100° C. for 10 min. The mixture was concentrated and purified with reverse phase HPLC (20-95% 0.1% TFA/AcCN in 0.1% TFA/H2O) affording 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidine-4-carboxylic acid (7.6 mg, 67%) as a yellow amorphous solid. MS (ESI, pos. ion) m/z: 405.2 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.03 (1H, d, J=2.3 Hz), 9.04 (1H, s), 8.40 (1H, d, J=2.7 Hz), 7.65-7.72 (2H, m), 7.59-7.64 (1H, m), 7.57 (1H, d, J=7.8 Hz), 3.83 (1H, dd, J=13.8, 6.6 Hz), 2.34 (1H, dt, J=7.9, 3.9 Hz), 1.29-1.36 (2H, m), 1.27 (6H, d, J=6.5 Hz), 1.23 (3H, dt, J=7.9, 3.2 Hz).

Workup

concentrationThe mixture was concentrated
custompurified with reverse phase HPLC (20-95% 0.1% TFA/AcCN in 0.1% TFA/H2O)

Sources & evidence

ORD record: ord-23e0de4e0ea8488ba01aefa5a16742f8
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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