Phosgene → HCID 59239501, compound

HRID 1697988Notes

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.O1CCOCC1.C(N(CC)CC)C.[C:44](Cl)(Cl)=[O:45].[NH2:48][C:49]1[CH:53]=[CH:52][O:51][N:50]=1>C1(C)C=CC=CC=1>[O:51]1[CH:52]=[CH:53][C:49]([NH:48][C:44]([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:45])=[N:50]1

Participants

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 (0.0795 g, 0.000197 mol) in dry 1,4-Dioxane (1.50 mL, 0.0192 mol) was added Triethylamine (0.0302 mL, 0.000217 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.120 mL). The reaction mixture was heated at 50° C. for 1 hour. The reaction mixture was cooled to room temperature and then added 3-aminoisoxazole (0.0874 mL, 0.00118 mol). The reaction mixture was stirred overnight. The reaction mixture was concentrated and purified by HPLC. 1H NMR (500 MHz, DMSO) δ 9.69 (s, 1H), 9.12 (s, 1H), 8.74 (d, J=1.6, 1H), 8.44 (d, J=4.7, 2H), 8.28 (d, J=8.7, 2H), 7.57 (d, J=8.7, 2H), 6.87 (d, J=1.7, 1H), 6.69 (t, J=4.7, 1H), 4.91 (d, J=18.6, 1H), 4.75 (d, J=18.7, 1H), 4.18-4.09 (m, 2H), 3.86 (dd, J=17.0, 9.4, 2H), 3.73-3.69 (m, 1H), 3.66-3.58 (m, 3H), 3.43 (t, J=10.8, 1H), 2.75 (s, 2H), 1.26 (d, J=6.7, 3H). LC/MS-m/z+514.2 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationThe reaction mixture was concentrated
custompurified by HPLC

Sources & evidence

ORD record: ord-09a4ba3c9cae406a8c9791ca939eeb5e
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163763B2

Reaction notes

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