Triethylamine → 3-chloro-8,8-dimethyl-1-(1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl-5,6-dihydro-8H-7-oxa-2,4,4b, 9-tetraaza-fluorene

HRID 334163Notes

Reaction equation

HRID 334163 reaction equation
Cl[C:2]1[C:14]2[N:13]=[C:12]3[N:7]([CH2:8][CH2:9][O:10][C:11]3([CH3:16])[CH3:15])[C:6]=2[N:5]=[C:4]([Cl:17])[N:3]=1.[C@H:18]12[CH2:24][C@H:21]([NH:22][CH2:23]1)[CH2:20][O:19]2.C(N(CC)CC)C>>[Cl:17][C:4]1[N:3]=[C:2]([N:22]2[CH2:23][C@@H:18]3[CH2:24][C@H:21]2[CH2:20][O:19]3)[C:14]2[N:13]=[C:12]3[N:7]([C:6]=2[N:5]=1)[CH2:8][CH2:9][O:10][C:11]3([CH3:16])[CH3:15]

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 11159293(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrobromideHCID 866673712,4-Dichloro-6,6-dimethyl-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purine

Product 1

HCID 866673743-chloro-8,8-dimethyl-1-(1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl-5,6-dihydro-8H-7-oxa-2,4,4b, 9-tetraaza-fluoreneYield 98%

Conditions

Temperature
140 °C

Procedure

A mixture of 1,3-dichloro-8,8-dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b,9-tetraaza-fluorene (100 mg, 0.366 mmol), (1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]heptane (73 mg, 0.732 mmol) and triethylamine (77 μL, 0.55 mmol) in IMS (2 mL) was heated at 140° C. for 20 mins in a microwave reactor, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, 10% ethyl acetate in pentane) affording 3-chloro-8,8-dimethyl-1-(1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl-5,6-dihydro-8H-7-oxa-2,4,4b, 9-tetraaza-fluorene as a yellow solid (120 mg, 98%). LCMS (method A): RT=2.81 min, [M+H]+=336.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting residue was purified by column chromatography (SiO2, 10% ethyl acetate in pentane)

Sources & evidence

ORD record
ord-45cc825b5d4b407bb6493cf7f46eb0bd
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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