Ethanolamine → 8-(aminomethyl)-10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]thiazine-2,4(3H,10H)-dione

HRID 2201231Notes

Reaction equation

C(CN)O.[Cl:5][C:6]1[O:10][C:9]([CH:11]2[C:16]3=[C:17]4[N:29]([CH3:30])[C:28](=[O:31])[N:27]([CH3:32])[C:26](=[O:33])[C:18]4=[C:19]([C:20]4[S:21][CH:22]=[C:23]([CH3:25])[N:24]=4)[N:15]3[CH2:14][CH:13]([CH2:34][N:35]3C(=O)C4C(=CC=CC=4)C3=O)[S:12]2)=[CH:8][CH:7]=1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[NH2:35][CH2:34][CH:13]1[S:12][CH:11]([C:9]2[O:10][C:6]([Cl:5])=[CH:7][CH:8]=2)[C:16]2=[C:17]3[N:29]([CH3:30])[C:28](=[O:31])[N:27]([CH3:32])[C:26](=[O:33])[C:18]3=[C:19]([C:20]3[S:21][CH:22]=[C:23]([CH3:25])[N:24]=3)[N:15]2[CH2:14]1

Participants

Conditions

Temperature: 70 °C

Procedure

Ethanolamine (0.320 mL, 5.30 mmol) was added to a solution of 10-(5-chlorofuran-2-yl)-8-((1,3-dioxoisoindolin-2-yl)methyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-7,8-dihydro-1H-pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,4]thiazine-2,4(3H,10H)-dione (537 mg, 0.883 mmol) in toluene (10 mL). The mixture was stirred at 70° C. for 3 hours and then cooled to room temperature for 16, then heated at 70° C. for a further 2.5 hours and again cooled to room temperature. The mixture was diluted with water (100 ml) and ethyl acetate (100 ml). The organic phase was separated, washed with 1M NaOH(aq) (50 ml) passed through a hydrophobic frit and evaporated under vacuum to afford the title compound as a mixture of diastereomers.

Workup

temperaturecooled to room temperature for 16
temperatureheated at 70° C. for a further 2.5 hours
temperatureagain cooled to room temperature
customThe organic phase was separated
washwashed with 1M NaOH(aq) (50 ml)
customevaporated under vacuum

Sources & evidence

ORD record: ord-d7c927ecb05646649337a38e80db6eec
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359381B2

Reaction notes

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