2-Chlorobenzoxazole → HCID 178429373, compound

HRID 707418Notes

Reaction equation

[NH2:1][C@H:2]1[CH2:5][C@H:4]([N:6]2[C:10]3=[N:11][CH:12]=[CH:13][N:14]=[C:9]3[C:8]([CH3:16])([CH3:15])[C:7]2=[O:17])[CH2:3]1.Cl[C:19]1[O:20][C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[O:20]1[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=[C:19]1[NH:1][C@H:2]1[CH2:5][C@H:4]([N:6]2[C:10]3=[N:11][CH:12]=[CH:13][N:14]=[C:9]3[C:8]([CH3:15])([CH3:16])[C:7]2=[O:17])[CH2:3]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a round bottomed flask was added 5-(trans-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (Intermediate 30, 0.1663 g, 0.716 mmol, [00391]), 2-chlorobenzo[d]oxazole (0.132 g, 0.859 mmol, Sigma-Aldrich Chemical Company, Inc.), and diisopropylethylamine (0.249 ml, 1.432 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (2.386 ml) to stir at 90° C. for 17 hours. The crude product was purified by reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over min. Product was taken up in DCM and loaded onto a Silicycle Si-carbonate cartridge to remove any salts to give 5-(trans-3-(benzo[d]oxazol-2-ylamino)cyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (32.2 mg, 0.092 mmol, 12.87% yield). LCMS showed product peak at 1.625 min (m+1=350.0). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (s, 6 H) 2.42-2.48 (m, 1 H) 3.18-3.29 (m, 2 H) 4.47-4.60 (m, 1 H) 5.17 (quin, J=8.31 Hz, 1 H) 6.95-7.04 (m, 1 H) 7.12 (td, J=7.63, 0.98 Hz, 1 H) 7.28 (d, J=7.24 Hz, 1 H) 7.37 (d, J=7.63 Hz, 1 H) 8.18 (d, J=3.33 Hz, 1 H) 8.23 (d, J=3.13 Hz, 1 H) 8.42 (d, J=6.65 Hz, 1 H).

Workup

customThe crude product was purified by reverse-phase preparative HPLC
customto remove any salts

Sources & evidence

ORD record: ord-3c5082ac47b44f99896d90cc7568429d
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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