Phosgene → HCID 59239532, compound

HRID 1697986Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][C@@H:22]3[CH3:27])[C:11]3[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1.[O:28]1[CH2:33]COCC1.C(N(CC)CC)C.C(Cl)(Cl)=O.[F:45][C:46]([F:50])([F:49])[CH2:47][NH2:48]>C1(C)C=CC=CC=1>[C:18]([N:15]1[CH2:16][CH2:17][C:11]2[C:10]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][C@@H:22]3[CH3:27])=[N:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:33]([NH:48][CH2:47][C:46]([F:50])([F:49])[F:45])=[O:28])=[CH:7][CH:6]=3)=[N:13][C:12]=2[CH2:14]1)(=[O:20])[CH3:19]

Participants

Conditions

Temperature: 50 °C

Procedure

Step 3—Synthesis of compound ux: (S)-1-(2-(4-aminophenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethanone (0.100 g, 0.000272 mol) in dry 1,4-Dioxane (2.00 mL, 0.0256 mol) was added Triethylamine (0.0416 mL, 0.000299 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.160 mL). The reaction mixture was heated at 50° C. for 1 hour. The reaction mixture was cooled to room temperature and then added 2,2,2-trifluoroethylamine (0.1280 mL, 0.001627 mol). The reaction mixture was stirred overnight. The reaction mixture was concentrated and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 9.01 (d, J=5.1, 1H), 8.21 (dd, J=8.8, 2.7, 2H), 7.52 (d, J=8.4, 2H), 6.82 (t, J=6.4, 1H), 4.74-4.43 (m, 2H), 4.16 (s, 1H), 4.00-3.85 (m, 3H), 3.64 (ddd, J=19.4, 16.7, 9.4, 6H), 3.43 (d, J=21.0, 2H), 2.76 (s, 1H), 2.63 (s, 1H), 2.12 (s, 3H), 1.33-1.22 (m, 3H). LC/MS-m/z+493.2 (M+H)+

Workup

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

Sources & evidence

ORD record: ord-0847ecadac8b4f878b52ea5d18f6f118
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163763B2

Reaction notes

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