Potassium Carbonate → N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-(cyclopropylmethoxy)-3-methylpyrazine-2-carboxamide

HRID 627759Notes

Reaction equation

[CH:1]1([CH2:4][O:5][C:6]2[N:7]=[C:8]([CH3:43])[C:9]([C:12]([NH:14][C:15]3[CH:16]=[CH:17][C:18]4[O:40][CH2:39][CH2:38][C@H:21]5[S:22](=[O:37])(=[O:36])[C:23]([CH3:35])([CH3:34])[C:24]([NH:26]C(=O)OC(C)(C)C)=[N:25][C@:20]5([CH3:41])[C:19]=4[CH:42]=3)=[O:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[NH2:26][C:24]1[C:23]([CH3:35])([CH3:34])[S:22](=[O:36])(=[O:37])[C@@H:21]2[CH2:38][CH2:39][O:40][C:18]3[CH:17]=[CH:16][C:15]([NH:14][C:12]([C:9]4[C:8]([CH3:43])=[N:7][C:6]([O:5][CH2:4][CH:1]5[CH2:2][CH2:3]5)=[CH:11][N:10]=4)=[O:13])=[CH:42][C:19]=3[C@@:20]2([CH3:41])[N:25]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a reaction mixture of tert-butyl ((4aR,11bR)-10-(5-(cyclopropylmethoxy)-3-methylpyrazine-2-carboxamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (40 mg, 0.065 mmol) in DMF 1 ml was added K2CO3 (40 mg, 0.29 mmol). It was heated to 85° C. for 3 h. It was cooled to RT, diluted with water, and extracted with EtOAc. The organic phase obtained was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 15% to 25% to 40% EtOAc/MeOH/Et3N in (40% EtOAc in Heptane) to yield 23 mg of desired product. MS m/z: 514.2 [M+H].

Workup

temperatureIt was cooled to RT
extractionextracted with EtOAc
customThe organic phase obtained
concentrationwas concentrated under reduced pressure
customthe residue was purified by silica gel chromatography
washeluting with 15% to 25% to 40% EtOAc/MeOH/Et3N in (40% EtOAc in Heptane)

Sources & evidence

ORD record: ord-a29b9fd9ba294ec3afcf6d37adcd9d46
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309263B2

Reaction notes

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