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

HRID 1697979Notes

Reaction equation

HRID 1697979 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.[C:48]([CH2:50][CH2:51][NH2:52])#[N:49]>C1(C)C=CC=CC=1>[C:48]([CH2:50][CH2:51][NH:52][C:36]([NH:18][C:17]1[CH:19]=[CH:20][C:14]([C:12]2[N:13]=[C:8]([N:7]3[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]3[CH3:1])[C:9]3[CH2:24][CH2:23][N:22]([C:25]4[N:26]=[CH:27][CH:28]=[CH:29][N:30]=4)[CH2:21][C:10]=3[N:11]=2)=[CH:15][CH:16]=1)=[O:31])#[N:49]

Participants

7

Reactant 5

HCID 16473-AminopropionitrileHCID 6371PhosgeneHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 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 59239388(S)-1-(2-cyanoethyl)-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 β-Cyanoethylamine (0.0546 mL, 0.000744 mol). The reaction mixture was stirred for 3 days. The reaction mixture was concentrated and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.98 (s, 1H), 8.44 (d, J=4.7, 2H), 8.22 (d, J=8.8, 2H), 7.52 (d, J=8.8, 2H), 6.69 (t, J=4.7, 1H), 6.62 (t, J=5.9, 1H), 4.90 (d, J=18.6, 1H), 4.73 (d, J=18.7, 1H), 4.19-4.06 (m, 2H), 3.92-3.77 (m, 2H), 3.73-3.67 (m, 1H), 3.60 (t, J=9.1, 3H), 3.43 (d, J=11.6, 1H), 3.36 (m, 2H), 2.80-2.63 (m, 4H), 1.25 (d, J=6.6, 3H). LC/MS-m/z+500.2 (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-46806647b1cc4afeb59f12f0afd7030b
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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