p-Toluenesulfonic acid monohydrate → N2-(4,5-dihydro-4,4-bis(methoxymethyl)tetrazolo[5,1-c][1,4]benzoxazin-8-yl)-N4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-yl)-5-fluoropyrimidin-2,4-diamine

HRID 633467Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:17][C@H:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[O:30][C:29]([CH2:34][O:35][CH3:36])([CH2:31][O:32][CH3:33])[C:28]3=[N:37][N:38]=[N:39][N:27]3[C:26]=2[CH:40]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>C(O)(C)C>[CH3:33][O:32][CH2:31][C:29]1([CH2:34][O:35][CH3:36])[C:28]2=[N:37][N:38]=[N:39][N:27]2[C:26]2[CH:40]=[C:22]([NH:21][C:2]3[N:7]=[C:6]([NH:8][C@@H:9]4[CH2:17][C@H:16]5[N:12]([CH2:13][CH2:14][CH2:15]5)[C:11]([CH3:19])([CH3:18])[CH2:10]4)[C:5]([F:20])=[CH:4][N:3]=3)[CH:23]=[CH:24][C:25]=2[O:30]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (7R,8aS)-N-(2-choro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (36 mg, 0.12 mmol, 1 equiv), 8-amino-4,4-bis(methoxymethyl)-4H-tetrazolo[5,1-c]-[1,4]-benzoxazine (40 mg, 0.14 mmol, 1.2 equiv) and pTsOH.H2O (46 mg, 0.24 mmol, 2.0 equiv) in isopropanol (1.0 mL) was heated at 100° C. overnight in a sealed vial. After allowing to cool to room temperature, the solvent was removed and the residue was purified by column chromatography using a mixture of DCM/2N NH3 in MeOH (95:5) to give the product as a solid.

Workup

temperatureto cool to room temperature
customthe solvent was removed
customthe residue was purified by column chromatography
additiona mixture of DCM/2N NH3 in MeOH (95:5)

Sources & evidence

ORD record: ord-94c14263960f4acfb72fc0165f1d7df3
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321763B2

Reaction notes

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