Morpholine → HCID 178420000, compound

HRID 707304Notes

Reaction equation

HRID 707304 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[N:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH2:12]1.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>>[O:29]1[CH2:30][CH2:31][N:26]([C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[C@H:11]2[CH2:14][C@H:13]([NH:15][C:16]3[N:25]=[CH:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]=3)[CH2:12]2)[CH2:27][CH2:28]1

Participants

3

Reactant 2

HCID 8083MorpholineHCID 178478378HCID 178478378, compound

Product 1

HCID 178420000HCID 178420000, compoundYield 48.8%

Conditions

Temperature
100 °C

Procedure

N-(Trans-3-(6-chloro-9H-purin-9-yl)cyclobutyl)quinazolin-2-amine (example 21, 0.0681 g, 0.194 mmol) was dissolved in morpholine (2.0 ml, 22.97 mmol) and heated in the microwave to 100° C. for 20 minutes. The solution was evaporated to dryness under reduced pressure and further dried under high vac. Purification using silica chromatography (0-10% methanol in dichloromethane gradient) gave the desired N-(trans-3-(6-morpholino-9H-purin-9-yl)cyclobutyl)quinazolin-2-amine (0.038 g, 0.094 mmol, 48.8% yield) as an off white solid. M+1: 403.2. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.80 (ddd, J=13.30, 8.31, 4.79 Hz, 2 H) 3.02-3.20 (m, 2 H) 3.85 (t, J=4.69 Hz, 4 H) 4.33 (br. s., 4 H) 4.78-4.94 (m, 1 H) 5.30 (quin, J=7.60 Hz, 1 H) 5.93 (br. s., 1 H) 7.23-7.34 (m, 1 H) 7.62 (d, J=8.22 Hz, 1 H) 7.66-7.75 (m, 2 H) 7.96 (s, 1 H) 8.37 (s, 1 H) 9.02 (s, 1 H).

Workup

  1. customThe solution was evaporated to dryness under reduced pressure
  2. customfurther dried under high vac
  3. customPurification

Sources & evidence

ORD record
ord-39d1546cf2044f0b894fb57f30abf603
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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