Phosgene → HCID 59239567, compound

HRID 1697984Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]3[CH3:26])[C:11]3[CH2:17][CH2:16][N:15]([CH:18]=[O:19])[CH2:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1.[O:27]1[CH2:32]COCC1.C(N(CC)CC)C.C(Cl)(Cl)=O.[F:44][C:45]([F:49])([F:48])[CH2:46][NH2:47]>C1(C)C=CC=CC=1>[CH:18]([N:15]1[CH2:16][CH2:17][C:11]2[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]3[CH3:26])=[N:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:32]([NH:47][CH2:46][C:45]([F:49])([F:48])[F:44])=[O:27])=[CH:7][CH:6]=3)=[N:13][C:12]=2[CH2:14]1)=[O:19]

Participants

Conditions

Temperature: 50 °C

Procedure

Step 3—Synthesis of compound uv: (S)-2-(4-aminophenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carbaldehyde (0.100 g, 0.000283 mol) in dry 1,4-Dioxane (2.00 mL, 0.0256 mol) was added Triethylamine (0.0434 mL, 0.000311 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.170 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 (0.1340 mL, 0.001703 mol). The reaction mixture was stirred overnight. The reaction mixture was concentrated and purified by HPLC. 1H NMR (500 MHz, DMSO) δ 9.01 (s, 1H), 8.27-8.17 (m, 3H), 7.52 (d, J=8.8, 2H), 6.81 (d, J=6.5, 1H), 4.66-4.39 (m, 2H), 4.08 (s, 1H), 3.93 (ddd, J=31.8, 19.1, 10.1, 3H), 3.78-3.53 (m, 6H), 3.50-3.40 (m, 2H), 2.73 (s, 1H), 2.64 (s, 1H), 1.25 (t, J=7.4, 3H). LC/MS-m/z+479.2 (M+H)+

Workup

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

Sources & evidence

ORD record: ord-d33baf68d6df4c8aaad865d9556a90fb
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163763B2

Reaction notes

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