Lithium hydroxide, monohydrate → HCID 86673091, compound

HRID 1853329Notes

Reaction equation

HRID 1853329 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][C:10]([C:15]1[N:20]=[CH:19][N:18]3[CH:21]=[CH:22][CH:23]=[C:17]3[CH:16]=1)=[CH:9][C:8]2=[N:24][O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:4].O.[OH-].[Li+]>O1CCCC1.CO.O>[C:26]([O:25][N:24]=[C:8]1[C:7]2[C:12](=[CH:13][CH:14]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=2)[O:11][C:10]([C:15]2[N:20]=[CH:19][N:18]3[CH:21]=[CH:22][CH:23]=[C:17]3[CH:16]=2)=[CH:9]1)([CH3:29])([CH3:27])[CH3:28]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86673092HCID 86673092, compound

Product 1

HCID 86673091HCID 86673091, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
60 °C

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 solvents were removed
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-7e8f15c6db87438ca4a20f3bdaf4cfb0
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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