Benzophenone imine → 4-(toluene-3-sulfonyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylamine

HRID 1054916Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:6][CH2:7][CH2:8][N:9]([S:12]([C:15]3[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:13])[C:10]=2[N:11]=1.C(=[NH:35])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:17]1([CH3:21])[CH:18]=[CH:19][CH:20]=[C:15]([S:12]([N:9]2[CH2:8][CH2:7][O:6][C:5]3[CH:4]=[CH:3][C:2]([NH2:35])=[N:11][C:10]2=3)(=[O:14])=[O:13])[CH:16]=1

Participants

Conditions

Temperature: 100 °C

Procedure

6-Bromo-4-(toluene-3-sulfonyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (300 mg, 0.81 mmol) was dissolved in p-dioxane (10 mL), followed by benzophenone imine (409 μL, 2.44 mmol), sodium tert-butoxide (207 mg, 2.15 mmol), XantPhos (70 mg, 0.12 mmol), and finally Pd2(dba)3 (74 mg, 0.08 mmol). The resulting mixture was heated to 100° C. for 2.5 hours. Then, the reaction mixture was concentrated under vacuum and partitioned in a mixture of ethyl acetate and water. The aqueous phase was discarded, and the organic phase was concentrated and purified by flash chromatography (12 g silica column, 0-60% EtOAc/Hexane) to give 4-(toluene-3-sulfonyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylamine Yield 80 mg (32%). LCMS (ESI): calc. C14H15N3O3S=305; obs. M+H=306.

Workup

concentrationThen, the reaction mixture was concentrated under vacuum
custompartitioned in a mixture of ethyl acetate and water
concentrationthe organic phase was concentrated
custompurified by flash chromatography (12 g silica column, 0-60% EtOAc/Hexane)

Sources & evidence

ORD record: ord-4c12c3b75a0d4c9da2acffbd308f83c6
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394315B2

Reaction notes

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