Triethylamine → (2R)-N-{(2R)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-hydroxyethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

HRID 896895Notes

Reaction equation

HRID 896895 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C@@H:7]([C:12]([OH:14])=O)[CH2:6][CH2:5]2.Cl.Cl.[NH2:17][CH2:18][C@@H:19]([C:21]1[CH:22]=[N:23][C:24]([N:27]2[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]2[CH3:33])=[CH:25][CH:26]=1)[OH:20].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.O>[CH3:33][C:28]1[N:27]([C:24]2[N:23]=[CH:22][C:21]([C@@H:19]([OH:20])[CH2:18][NH:17][C:12]([C@H:7]3[CH2:6][CH2:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=4)[O:8]3)=[O:14])=[CH:26][CH:25]=2)[C:31]([CH3:32])=[CH:30][CH:29]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 9966213(2R)-6-Iodochromane-2-carboxylic acidHCID 69141211(1R)-2-amino-1-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]ethanol dihydrochloride

Product 1

HCID 59118220(2R)-N-{(2R)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]-2-hydroxyethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A reaction mixture containing (2R)-6-iodo-3,4-dihydro-2H-chromene-2-carboxylic acid (Example 7, 5.39 mmol, 1.0 eq.), (1R)-2-amino-1-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]ethanol dihydrochloride (U.S. Pat. No. 6,051,586) (6.47 mmol, 1.2 eq.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl, 10.8 mmol, 2.0 eq.), 1-hydroxybenzotriazole hydrate (HOBT, 10.8 mmol, 2.0 eq.), and triethylamine (16.2 mmol, 3.0 eq.) in CH2Cl2 (30 mL) was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the resulting two-phase mixture was extracted with CH2Cl2. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, concentrated and purified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, CH2Cl2:MeOH=100:4). The product was obtained as a pale yellow foam in 56% yield. MH+=518.2, RT=3.74 min.

Workup

  1. extractionthe resulting two-phase mixture was extracted with CH2Cl2
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. custompurified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, CH2Cl2:MeOH=100:4)
  6. customThe product was obtained as a pale yellow foam in 56% yield

Sources & evidence

ORD record
ord-9e75a1eb266a43fcbc74c14d120535d9
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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