Cesium carbonate → 2-Cyclopropyl-6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 2284436Notes

Reaction equation

HRID 2284436 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:22])[N:11]2[C:16]=1[C:15]([N:17]1[CH:21]=NC=N1)=[N:14][CH:13]=[N:12]2.[CH:23]1([C:26]2[N:27]=[CH:28][C:29]3[CH2:35]NC[CH2:32][C:30]=3[N:31]=2)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH:23]1([C:26]2[N:27]=[CH:28][C:29]3[CH2:35][N:17]([C:15]4[C:16]5=[C:8]([C:3]6[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=6[F:1])[N:9]=[C:10]([CH3:22])[N:11]5[N:12]=[CH:13][N:14]=4)[CH2:21][CH2:32][C:30]=3[N:31]=2)[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 223084332-cyclopropyl-5H,6H,7H,8H-pyrido[4,3-d]pyrimidineHCID 1176784165-(2-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine

Product 1

HCID 917995362-Cyclopropyl-6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of C6 (6.40 g, 21.7 mmol), 2-cyclopropyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (3.84 g, 21.9 mmol) and cesium carbonate (7.06 g, 21.7 mmol) was stirred in N,N-dimethylformamide (45 mL) for 2 hours at room temperature. The reaction mixture was concentrated in vacuo, then stirred with water (45 mL) for 18 hours. Filtration provided the product as an off-white powder. Yield: 6.68 g, 16.6 mmol, 76%. This material was combined with product from two similar runs (total weight: 20.37 g) and triturated with a mixture of heptane (100 mL) and ethyl acetate (100 mL) for 3 days at room temperature. Filtration provided the product as an off-white powder (19.6 g). LCMS m/z 402.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 7.97 (s, 1H), 7.92 (br s, 1H), 7.63 (ddd, J=7.6, 7.4, 1.8 Hz, 1H), 7.36-7.41 (m, 1H), 7.27 (ddd, J=7.6, 7.6, 1.1 Hz, 1H), 7.07 (br ddd, J=9, 9, 1 Hz, 1H), 4.51 (s, 2H), 3.86-3.90 (m, 2H), 2.73 (s, 3H), 2.71-2.76 (m, 2H), 2.12-2.18 (m, 1H), 1.00-1.08 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. filtrationFiltration

Sources & evidence

ORD record
ord-cf144974c8ed45c29b4ef84311a19371
Source dataset
uspto-grants-2015_09
Patent number
US09145427B2

Reaction notes

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