Morpholine → 2-Chloro-7-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

HRID 528470Notes

Reaction equation

HRID 528470 reaction equation
[CH:1]1([CH:4]2[O:15][C:8]3[N:9]=[C:10]([Cl:14])[N:11]=[C:12](Cl)[C:7]=3[O:6][CH2:5]2)[CH2:3][CH2:2]1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(N(CC)CC)C>>[Cl:14][C:10]1[N:11]=[C:12]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:7]2[O:6][CH2:5][CH:4]([CH:1]3[CH2:3][CH2:2]3)[O:15][C:8]=2[N:9]=1

Participants

4

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 867117537-Cyclopropyl-2,4-dichloro-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Product 1

HCID 867117542-Chloro-7-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidineYield 87%

Conditions

Temperature
140 °C

Procedure

A mixture of 7-cyclopropyl-2,4-dichloro-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (93 mg, 0.40 mmol), morpholine (150 μL, 1.71 mmol) and triethylamine (80 μL, 0.57 mmol) in IMS (3 mL) was heated at 140° C. for 35 minutes using microwave irradiation before being concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, 0-20% ethyl acetate in cyclohexane) affording 2-Chloro-7-cyclopropyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (98 mg, 87%). LCMS: RT=3.02 min, [M+H]+=284/286.

Workup

  1. custommicrowave irradiation
  2. concentrationbefore being concentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (SiO2, 0-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-c1b58698202b45438eed2dfffe797629
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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