Triethylamine → HCID 123959330, compound

HRID 1853330Notes

Reaction equation

HRID 1853330 reaction equation
[C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]([OH:19])=O)[CH:15]=2)[O:10][C:9]([C:20]2[N:25]=[CH:24][N:23]3[CH:26]=[CH:27][CH:28]=[C:22]3[CH:21]=2)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:59][CH2:60][CH2:61][N:62]1[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1>CN(C)C=O>[N:62]1([CH2:61][CH2:60][NH:59][C:17]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[O:10][C:9]([C:20]2[N:25]=[CH:24][N:23]4[CH:26]=[CH:27][CH:28]=[C:22]4[CH:21]=2)=[CH:8][C:7]3=[N:6][O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:19])[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 4082852-MorpholinoethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86673091HCID 86673091, compound

Product 1

HCID 123959330HCID 123959330, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 4-(tert-Butoxyimino)-2-pyrrolo[1,2-c]pyrimidin-3-yl-4H-chromene-6-carboxylic acid methyl ester (example 115B) (170 mg, 0.43 mmol) in a mixture of tetrahydrofuran/methanol/water (2.0 ml/0.5 ml/0.5 ml) was treated with lithium hydroxide monohydrate (55 mg, 1.29 mmol) and heated at 60° C. for 2 hours. The solvents were removed and the residue was diluted with water, neutralized to pH 5-6 with a 1N solution of hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to dryness to give 4-(tert-Butoxyimino)-2-pyrrolo[1,2-c]pyrimidin-3-yl-4H-chromene-6-carboxylic acid (135 mg, 84%) as a green solid. A solution of the previous carboxylic acid, (3-Dimethylamino-propyl)-ethyl-carbodiimide, hydrochloride (90 mg, 0.47 mmol), 1-Hydroxybenzotriazole hydrate (68 mg, 0.50 mmol) and triethylamine (250 μl, 1.80 mmol) in dimethylformamide (6.0 ml) was stirred at 0° C. for 1 hour then 4-(2-aminoethyl)-morpholine (52 μl, 0.40 mmol) was added. The mixture was stirred at room temperature for 18 hours. The volatiles were removed under vacuum and the residue taken into ethyl acetate, washed several times with a saturated solution of sodium hydrogenocarbonate, brine, dried over sodium sulfate and concentrated to dryness. The residue was purified by silica gel flash chromatography (gradient ethyl acetate/methanol 0-8%) to yield the title compound as a yellow solid (137 mg, 78%).

Workup

  1. customThe volatiles were removed under vacuum
  2. washwashed several times with a saturated solution of sodium hydrogenocarbonate, brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by silica gel flash chromatography (gradient ethyl acetate/methanol 0-8%)

Sources & evidence

ORD record
ord-8af949c658e24a399dd82c7bacb039ff
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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