Lithium Hydroxide → HCID 131729425, compound

HRID 425396Notes

Reaction equation

HRID 425396 reaction equation
[OH-].[Li+].[C:3]([NH:6][CH:7]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:15][CH:14]=1)[C:8](OC)=[O:9])(=[O:5])[CH3:4].C(=O)(O)[O-].[Na+].[NH2:38][CH2:39][CH:40]([OH:47])[CH2:41][C:42]([CH3:46])([CH3:45])[CH2:43][CH3:44].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>O1CCCC1.O.O.C(Cl)Cl>[C:29]([O:28][C:26](=[O:27])[NH:25][C:20]1[C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH2:12][CH:7]([NH:6][C:3](=[O:5])[CH3:4])[C:8]([NH:38][CH2:39][CH:40]([OH:47])[CH2:41][C:42]([CH3:46])([CH3:45])[CH2:43][CH3:44])=[O:9])=[CH:14][CH:15]=2)=[CH:23][N:22]([CH3:24])[N:21]=1)([CH3:31])([CH3:30])[CH3:32]

Participants

10

Reactant 6

HCID 3939Lithium HydroxideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55289824HCID 55289824, compoundHCID 66705663methyl 2-(acetylamino)-3-(4-{3-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrazol-4-yl}phenyl)propanoate

Product 1

HCID 131729425HCID 131729425, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

Lithium hydroxide (444 mg, 10.8 mmol) was added to an ambient temperature solution of methyl 2-(acetylamino)-3-(4-{3-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrazo 1-4-yl}phenyl)propanoate (450 mg, 1.08 mmol) in tetrahydrofuran/water (10:1) (11 mL). After stirring at ambient temperature for 1 h, the reaction mixture was diluted with water and extracted with ethyl acetate. The aqueous phase was acidified with 1.5 N hydrochloric acid and extracted with ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Sodium bicarbonate (727 mg, 8.66 mmol) was added to an ambient temperature solution of the crude residue, 1-amino-4,4-dimethylhexan-2-ol (314 mg, 2.16 mmol), 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (415 mg, 2.16 mmol) and 1-hydroxybenzotriazole (292 mg, 2.16 mmol) in methylene chloride (20 mL). After stirring at ambient temperature overnight, the reaction was quenched with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-100% ethyl acetate/hexane afforded tert-butyl[4-(4-{2-(acetylamino)-3-[(2-hydroxy-4,4-dimethylhexyl)amino]-3-oxopropyl}phenyl)-1-methyl-1H-pyrazol-3-yl]carbamate.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. concentrationconcentrated in vacuo
  5. stirringAfter stirring at ambient temperature overnight
  6. customthe reaction was quenched with water
  7. extractionextracted with methylene chloride and ethyl acetate
  8. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5d6538de3d7a408980d87525ea0b714b
Source dataset
uspto-grants-2012_01
Patent number
US08106070B2

Reaction notes

Loading…