Phosgene → HCID 59239504, compound

HRID 1697992Notes

Reaction equation

HRID 1697992 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[CH:30]=[CH:29][N: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:16]=[CH:15][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[CH:30]=[CH:29][N:28]=[CH:27][N:26]=5)[CH2:21][C:10]=4[N:11]=3)=[CH:20][CH:19]=2)=[O:31])[CH2:52][CH2:51][CH2:50]1

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 75645CyclobutylamineHCID 68555623HCID 68555623, compound

Product 1

HCID 59239504HCID 59239504, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

(S)-4-(4-(3-methylmorpholino)-7-(pyrimidin-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)aniline (0.0700 g, 0.000173 mol) in dry 1,4-Dioxane (1.50 mL, 0.0192 mol) was added Triethylamine (0.0266 mL, 0.000191 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.100 mL). The reaction mixture was heated at 50° C. for 1 hour. The reaction mixture was cooled to room temperature and then added aminocyclobutane (0.0892 mL, 0.00104 mol). The reaction mixture was stirred overnight. LC-MS shows mostly product. The reaction mixture was concentrated purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 8.56 (s, 1H), 8.22 (dd, J=16.1, 7.5, 3H), 7.48 (d, J=8.8, 2H), 6.96 (d, J=6.2, 1H), 6.57 (d, J=7.6, 1H), 4.76 (d, J=18.0, 1H), 4.64 (d, J=18.3, 1H), 4.15 (dt, J=15.6, 7.8, 2H), 4.00 (dd, J=16.4, 8.3, 1H), 3.87 (d, J=11.3, 1H), 3.80-3.57 (m, 5H), 2.75 (s, 2H), 2.20 (dt, J=14.1, 5.0, 2H), 2.10 (ddd, J=10.1, 7.6, 3.6, 1H), 1.93-1.79 (m, 2H), 1.73 (dt, J=11.9, 9.7, 1H), 1.56 (m, 2H), 1.26 (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-04ddf3e6ff5e445ba605947d6528c178
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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