Phosgene → (S)-1-cyclobutyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea

HRID 1697980Notes

Reaction equation

HRID 1697980 reaction equation
[CH3:1][C@@H:2]1[N:7]([C:8]2[C:9]3[CH2:24][CH2:23][N:22]([C:25]4[N:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[CH2:21][C:10]=3[N:11]=[C:12]([C:14]3[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=3)[N:13]=2)[CH2:6][CH2:5][O:4][CH2:3]1.[O:31]1[CH2:36]COCC1.C(N(CC)CC)C.C(Cl)(Cl)=O.[NH2:48][CH:49]1[CH2:52][CH2:51][CH2:50]1>C1(C)C=CC=CC=1>[CH:49]1([NH:48][C:36]([NH:18][C:17]2[CH:19]=[CH:20][C:14]([C:12]3[N:13]=[C:8]([N:7]4[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]4[CH3:1])[C:9]4[CH2:24][CH2:23][N:22]([C:25]5[N:26]=[CH:27][CH:28]=[CH:29][N:30]=5)[CH2:21][C:10]=4[N:11]=3)=[CH:15][CH:16]=2)=[O:31])[CH2:52][CH2:51][CH2:50]1

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 75645CyclobutylamineHCID 67176513(S)-4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)aniline

Product 1

HCID 59239053(S)-1-cyclobutyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

(S)-4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)aniline (0.0501 g, 0.000124 mol) in dry 1,4-Dioxane (2.00 mL, 0.0256 mol) was added Triethylamine (0.0190 mL, 0.000136 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.080 mL). The reaction mixture was heated at 50° C. for 1 hour. The reaction mixture was cooled to room temperature and then added aminocyclobutane (0.0638 mL, 0.000745 mol). The reaction mixture was stirred for 3 days. The reaction mixture was concentrated and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.59 (s, 1H), 8.43 (d, J=4.7, 2H), 8.20 (d, J=8.8, 2H), 7.48 (d, J=8.8, 2H), 6.69 (t, J=4.7, 1H), 6.51 (d, J=8.1, 1H), 4.89 (d, J=18.7, 1H), 4.72 (d, J=18.7, 1H), 4.21-4.03 (m, 3H), 3.91-3.78 (m, 2H), 3.70 (dd, J=11.2, 2.7, 1H), 3.60 (t, J=9.2, 3H), 3.41 (t, J=12.7, 1H), 2.74 (s, 2H), 2.20 (dt, J=14.3, 5.1, 2H), 1.92-1.77 (m, 2H), 1.60 (ddd, J=21.1, 13.6, 8.3, 2H), 1.25 (d, J=6.6, 3H). LC/MS-m/z+501.3 (M+H)+

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by HPLC

Sources & evidence

ORD record
ord-c5b88972bc3d4b568f1df719e357f3de
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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