Triethylamine → methyl 7-(4-(chroman-3-ylcarbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate

HRID 510670Notes

Reaction equation

HRID 510670 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[O:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][CH:53]([NH2:61])[CH2:52]1.C(N(CC)CC)C>ClCCCl>[O:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][CH:53]([NH:61][C:18]([C:17]2[CH:21]=[CH:22][C:14]([O:13][C:12]3[CH:11]=[C:10]4[C:5]([CH:6]([C:23]([O:25][CH3:26])=[O:24])[CH2:7][CH2:8][O:9]4)=[CH:4][C:3]=3[C:1]#[N:2])=[CH:15][CH:16]=2)=[O:20])[CH2:52]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 2057083,4-dihydro-2H-1-benzopyran-3-amine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 462211084-(6-Cyano-4-(methoxycarbonyl)-chroman-7-yloxy)benzoic acid

Product 1

HCID 67080409methyl 7-(4-(chroman-3-ylcarbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylateYield 65.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A mixture of 4-(6-cyano-4-(methoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 2) (0.0308 g, 0.0871 mmol), 1-(3-(dimethylamino)propyl)-3-ethyl-carbodiimide hydrochloride (0.01838 g, 0.0958 mmol), 1-hydroxybenzotriazole monohydrate (0.0146 g, 0.095 mmol), and 1,2-dichloroethane (1 ml) was stirred at ambient temperature for 20 minutes. A mixture of chroman-3-amine hydrochloride (0.01780 g, 0.09589 mmol), triethylamine (0.06075 ml, 0.435 mmol), and 1,2-dichloroethane (1 ml) was added to the activated acid and the mixture was stirred for 17 hours at ambient temperature. The crude mixture was purified on silica gel (MeOH in dichloromethane gradient) to provide 27.6 mg of the title compound as a foamy film (65%)

Workup

  1. additionwas added to the activated acid
  2. stirringthe mixture was stirred for 17 hours at ambient temperature
  3. customThe crude mixture was purified on silica gel (MeOH in dichloromethane gradient)

Sources & evidence

ORD record
ord-afa21948215642fd9b72f6bde3b33230
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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