Triethylamine → HCID 52916787, compound

HRID 2063381Notes

Reaction equation

HRID 2063381 reaction equation
[CH:1]1([C:4]2[N:5]([CH2:27][CH3:28])[C:6]3[C:11]([N:12]=2)=[C:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:9]=[C:8]([C:20]2[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=2)[N:7]=3)[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:37](Cl)([O:39]C(=O)OC(Cl)(Cl)Cl)Cl.[O:48]1[CH2:51][CH:50]([NH2:52])[CH2:49]1>ClCCCl.C(OCC)(=O)C>[CH:1]1([C:4]2[N:5]([CH2:27][CH3:28])[C:6]3[C:11]([N:12]=2)=[C:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:9]=[C:8]([C:20]2[CH:21]=[CH:22][C:23]([NH:24][C:37]([NH:52][CH:50]4[CH2:51][O:48][CH2:49]4)=[O:39])=[CH:25][CH:26]=2)[N:7]=3)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 98339233-OxetanamineHCID 58222541HCID 58222541, compound

Product 1

HCID 52916787HCID 52916787, compoundYield 46.5%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-4-(8-cyclopropyl-9-ethyl-6-(3-methylmorpho-lino)-9H-purin-2-yl)aniline (52.0 mg, 0.14 mmol) in anhydrous 1,2-dichloroethane (3.0 mL) was added triethylamine (0.063 mL, 0.45 mmol, 3.3 eq.). The reaction was cooled to 0° C. and triphosgene (40.8 mg, 0.14 mmol, 1.0 eq) was added in one portion. After stirring at 0° C. under N2 for 5 minutes, the reaction mixture was stirred at 70° C. for 1 h. The reaction mixture was cooled to RT, and 3-oxetanamine (50.2 mg, 0.69 mmol, 5.0 eq.) was then added. The reaction mixture was stirred at RT under N2 for 16 h and then diluted with ethyl acetate (25 mL). The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified by reverse phase HPLC to give the title compound as a white solid (30.5 mg, 46.5%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.78 (s, 1H), 8.24 (d, J=8.7 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 6.97 (d, J=6.7 Hz, 1H), 5.37 (broad s, 1H), 5.03 (broad s, 1H), 4.86 to 4.69 (m, 3H), 4.44 (t, J=6.0 Hz, 2H), 4.35 (q, J=7.1 Hz, 2H), 3.97 (d, J=8.7 Hz, 1H), 3.77 (d, J=11.3 Hz, 1H), 3.68 (dd, J=11.4 Hz, 2.6 Hz, 1H), 3.53 (t, J=10.5 Hz, 1H), 3.44 to 3.33 (m, 1H), 2.30 to 2.19 (m, 1H), 1.39 (t, J=7.2 Hz, 3H), 1.28 (d, J=6.7 Hz, 3H), 1.10 to 0.95 (m, 4H); LC-MS m/z (method C)=478.2 [M+H]+, RT=4.44 min.

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for 1 h
  2. temperatureThe reaction mixture was cooled to RT
  3. stirringThe reaction mixture was stirred at RT under N2 for 16 h
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-68bd566ed6fd4aed86c540226bd09ab3
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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