N-(3-Aminopropyl)morpholine → HCID 59508063, compound

HRID 1958643Notes

Reaction equation

HRID 1958643 reaction equation
[CH3:1][O:2][C:3]1[C:8]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([C:18]([OH:20])=O)=[CH:13][CH:12]=3)=[CH:7][CH:6]=[CH:5][N:4]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[O:54]1[CH2:59][CH2:58][N:57]([CH2:60][CH2:61][CH2:62][NH2:63])[CH2:56][CH2:55]1>CN(C)C=O>[CH3:1][O:2][C:3]1[C:8]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([C:18]([NH:63][CH2:62][CH2:61][CH2:60][N:57]2[CH2:58][CH2:59][O:54][CH2:55][CH2:56]2)=[O:20])=[CH:13][CH:12]=3)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 61055N-(3-Aminopropyl)morpholineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59508110HCID 59508110, compound

Product 1

HCID 59508063HCID 59508063, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2-methoxypyridin-3-yl)-1H-indole-5-carboxylic acid (0.850 g, 0.317 mmol) in dimethylformamide (5 ml) was added HBTU (1.20 g, 0.317 mmol) and N,N-diisopropylethylamine (0.70 ml, 0.519 g, 0.402 mmol). The reaction mixture was allowed to stir for five minutes and 3-morpholinopropan-1-amine (0.59 ml) was added. The reaction was allowed to stir for 2 hours at room temperature. The reaction was quenched by adding water (25 ml), saturated sodium bicarbonate solution (25 ml) and extracted with EtOAc (2×50 ml). The organic extracts were combined, washed with brine (1×25 ml), dried over sodium sulfate and concentrated. The crude product was purified by flash column chromatography (SiO2, 100% EtOAc to 3% MeOH in EtOAc) to give the desired product as a white solid (1.09 g, 87%). M.p.=224-225° C.; 400 MHz 1H NMR (DMSO-d6) δ: 11.55 (s, 1H), 8.36 (t, J=5.4 Hz, 1H), 8.23 (dd, J=1.6 Hz, 7.6 Hz, 1H), 8.17 (dd, J=2.0 Hz, 5.2 Hz, 1H), 8.11 (s, 1H), 7.65 (dd, J=2 Hz, 8.4 Hz, 1H), 7.47 (d, J=8.4, 1H), 7.18-7.12 (m, 2H), 4.06 (s, 3H), 3.60-3.56 (m, 4H), 3.35-3.27 (m, 2H), 2.38-2.31 (m, 6H), 1.76-1.66 (m, 2H); LCMS: 395 [M+H]. Hydrolysis as described in General Procedure O provides compound 55 in Table 2.

Workup

  1. stirringto stir for 2 hours at room temperature
  2. customThe reaction was quenched
  3. additionby adding water (25 ml), saturated sodium bicarbonate solution (25 ml)
  4. extractionextracted with EtOAc (2×50 ml)
  5. washwashed with brine (1×25 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography (SiO2, 100% EtOAc to 3% MeOH in EtOAc)

Sources & evidence

ORD record
ord-441489d556e046679e8aebea96bc8325
Source dataset
uspto-grants-2013_04
Patent number
US08410144B2

Reaction notes

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