1H-Indole-3-propanoic acid → HCID 118307334, compound

HRID 1483227Notes

Reaction equation

HRID 1483227 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][C:8]2[C:11]([C:25]([NH2:27])=[O:26])=[C:12]([NH:14][C:15](=[O:24])[NH:16][C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[S:13][C:7]=2[CH2:6]1.C(N(CC)CC)C.[NH:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37]([CH2:44][CH2:45][C:46](O)=[O:47])=[CH:36]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:15]([NH:14][C:12]2[S:13][C:7]3[CH2:6][N:5]([CH2:4][CH2:3][CH2:2][NH:1][C:46](=[O:47])[CH2:45][CH2:44][C:37]4[C:38]5[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=5)[NH:35][CH:36]=4)[CH2:10][CH2:9][C:8]=3[C:11]=2[C:25]([NH2:27])=[O:26])=[O:24])=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 37441H-Indole-3-propanoic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 118307375HCID 118307375, compound

Product 1

HCID 118307334HCID 118307334, compoundYield 38.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 6-(3-aminopropyl)-2-{[(4-chlorophenyl)carbamoyl]amino}-4H,5H,6H,7H-thieno[2,3-c]pyridine-3-carboxamide (0.14 mmol) in anhydrous THF (1.5) were added triethyl amine (93 μL, 0.66 mmol), 3-indolepropionic acid (31 mg, 0.16 mmol), EDC.HCl (31 mg, 0.16 mmol), HOBt (25 mg, 0.16 mmol) and the resultant mixture was stirred at room temperature for 8 h. Upon completion, the solvent was removed in vacuo and the oil was taken up in DCM. The organics were washed with water (×2) and dried (anhydrous Na2SO4) and evaporated to afford the crude product which was purified by flash chromatography Isolera system (SiO2 gel as stationary phase, 12 g HP column, dry loading) using DCM-DCM/MeOH (0%-12% MeOH in DCM) to afford the title compound as a brown solid (31 mg, 37% yield). 1H NMR (300 MHz, MeOH-d4) δ 7.55 (d, J=15.5 Hz, 1H), 7.50-7.43 (m, 2H), 7.34-7.24 (m, 3H), 7.12-6.95 (m, 3H), 3.38 (bs, 2H), 3.17 (t, J=6.7 Hz, 2H), 3.06 (t, J=7.2 Hz, 2H), 2.82-2.74 (m, 2H), 2.68-2.61 (m, 2H), 2.55 (t, J=7.2 Hz, 2H), 2.36-2.27 (m, 2H), 1.67-1.54 (m, 2H). LRMS [M+H]579.

Workup

  1. customUpon completion, the solvent was removed in vacuo
  2. washThe organics were washed with water (×2)
  3. dry with materialdried (anhydrous Na2SO4)
  4. customevaporated
  5. customto afford the crude product which
  6. customwas purified by flash chromatography Isolera system (SiO2 gel as stationary phase, 12 g HP column, dry loading)

Sources & evidence

ORD record
ord-7882a503c76646aeaa692b1f6c7bafe8
Source dataset
uspto-grants-2016_08
Patent number
US09416141B2

Reaction notes

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