N-methyl-2-pyrrolidone → (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-amine

HRID 1261875Notes

Reaction equation

HRID 1261875 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1.[Br:17][C:18]1[N:26]2[C:21]([CH:22]=[N:23][C:24](S(C)=O)=[N:25]2)=[CH:20][CH:19]=1.CN1CCCC1=O>>[Br:17][C:18]1[N:26]2[C:21]([CH:22]=[N:23][C:24]([NH:16][C:13]3[CH:14]=[CH:15][C:8]4[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:11][CH2:10][C:9]=4[CH:12]=3)=[N:25]2)=[CH:20][CH:19]=1

Participants

4

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 580713077-Bromo-2-(methylsulfinyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 66712060(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-amineYield 65%

Conditions

Temperature
135 °C

Procedure

Into a 30 ml, vial, [A] 3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (0.242 g, 0.00110 mol), [B] 7-Bromo-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazine (0.130 g, 0.000500 mol), and N-Methylpyrrolidinone (0.39 mL, 0.0041 mol) were added. The reaction mixture was heated at 135° C. for 7 hours. The reaction mixture was purified via ISCO column chromatography with EtOAc and methanol as eluant (5 to 20% methanol). The collected fractions afforded (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-amine as a yellow solid (130 mg, 65%). NMR 1H (CDCl3-d)-8.57 (s, 1H), 7.54 (s, 1H), 7.48 (dd, 1H, JJ=1.96, 6.04 Hz), 7.69 (s, 1H), 7.09 (d, 1H, J=8.04 Hz), 6.93 (s, 1H), 6.78 (d, 1H, J=4.72 Hz), 6.73 (d, 1H, J=4.72 Hz), 3.54 (t, 2H, J=5.68 Hz), 3.36 (s, 3H), 2.65-3.00 (m, 10H)

Workup

  1. customThe reaction mixture was purified via ISCO column chromatography with EtOAc and methanol as eluant (5 to 20% methanol)

Sources & evidence

ORD record
ord-da01dacdc4a644f288e33b78474cdbd9
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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