4-Methylmorpholine → HCID 86661691, compound

HRID 1262269Notes

Reaction equation

HRID 1262269 reaction equation
[CH2:1]([NH2:4])[C:2]#[CH:3].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42]3[N:47]=[CH:46][C:45]4=[CH:48][CH:49]=[C:50]([C:51]5[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=5)[C:54](O)=[O:55])[N:44]4[N:43]=3)=[CH:37][CH:36]=2)[CH2:31][CH2:30]1.CN1CCOCC1>CN(C)C=O.C([O-])(O)=O.[Na+]>[CH3:28][N:29]1[CH2:30][CH2:31][N:32]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42]3[N:47]=[CH:46][C:45]4=[CH:48][CH:49]=[C:50]([C:51]5[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=5)[C:54]([NH:4][CH2:1][C:2]#[CH:3])=[O:55])[N:44]4[N:43]=3)=[CH:37][CH:36]=2)[CH2:33][CH2:34]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 239041PropargylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66712755HCID 66712755, compound

Product 1

HCID 86661691HCID 86661691, compoundYield 34.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Into a 8-dram vial, Prop-2-ynylamine (0.0643 g, 0.00117 mol) was dissolved in N,N-Dimethylformamide (1.75 mL), and 1-Hydroxybenzotriazole hydrate (0.0429 g, 0.000280 mol), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (53.7 mg, 0.280 mmol) were added. After stirring for 5 min, 3-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzoic acid (100 mg, 0.233 mmol) was added followed by 4-Methylmorpholine (0.0308 mL, 0.280 mmol). The reaction was stirred at rt for 1 hour. The reaction mixture was diluted with NaHCO3 and the resulting ppt was filtered, washed with NaHCO3 and water. The solid was dried under vacuum to give 3-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-N-prop-2-ynyl-benzamide as a yellow solid (37 mg, 34%). LCMS (E/I+) 466.19 (M+H). MP 185-187° C. NMR 1H (DMSO-d6)-9.25 (s, 1H), 9.03 (t, 1H, J=4.84 Hz), 8.96 (s, 1H), 8.57 (s, 1H), 8.39 (d, 1H, J=8.02 Hz), 7.84 (d, 1H, J=8.02 Hz), 7.65 (d, 1H, J=8.02 Hz), 7.62 (d, 2H, J=8.32 Hz), 7.20 (d, 1H, J=4.75 Hz), 6.95 (d, 1H, J=4.75 Hz), 6.89 (d, 2H, J=8.00 Hz), 4.11 (s, 2H), 3.14 (s, 1H), 3.06 (bs, 4H), 2.46 (bs, 4H), 2.22 (s, 3H).

Workup

  1. stirringThe reaction was stirred at rt for 1 hour
  2. filtrationthe resulting ppt was filtered
  3. washwashed with NaHCO3 and water
  4. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-3df21032f94f40b5932aa7bd5950792d
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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