Water → HCID 86707299, compound

HRID 576090Notes

Reaction equation

HRID 576090 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[C:5]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([N:18]2[CH2:27][CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([S:28]([N:31]([C:41]4[CH:46]=[CH:45][C:44]([CH2:47][CH2:48][CH2:49][CH:50]5[CH2:54][CH2:53][CH2:52][CH2:51]5)=[CH:43][C:42]=4[F:55])[CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)(=[O:30])=[O:29])[CH:24]=3)[CH2:19]2)=O)=[CH:11][CH:10]=1)([CH3:8])([CH3:7])[CH3:6].O.[Cl-].[NH4+]>O1CCCC1.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[C:5]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2([N:18]3[CH2:27][CH2:26][C:25]4[C:20](=[CH:21][CH:22]=[C:23]([S:28]([N:31]([C:41]5[CH:46]=[CH:45][C:44]([CH2:47][CH2:48][CH2:49][CH:50]6[CH2:54][CH2:53][CH2:52][CH2:51]6)=[CH:43][C:42]=5[F:55])[CH2:32][C:33]5[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=5)(=[O:29])=[O:30])[CH:24]=4)[CH2:19]3)[CH2:2][CH2:1]2)=[CH:11][CH:10]=1)([CH3:8])([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 86707300HCID 86707300, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 86707299HCID 86707299, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Tetraisopropyl orthotitanate (97 μL, 0.33 mmol) and ethyl magnesium bromide (diethyl ether solution, 3 mol/L, 0.25 mL, 0.75 mmol) were added to a solution of 2-[(4-tert-butylphenyl)acetyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-N-(4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide obtained (213 mg, 0.30 mmol) in tetrahydrofuran (5 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature for 16 hr. Water and saturated aqueous ammonium chloride solution were added to the reaction mixture and the mixture was stirred and then filtered through Celite (registered trademark). The filtrate was concentrated under reduced pressure, 1 mol/mL aqueous sodium hydroxide solution was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The desiccant was filtered off, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (hexane only→hexane:ethyl acetate=3:2) to afford 2-[1-(4-tert-butylbenzyl)cyclopropyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-N-(4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide as a pale yellow amorphous substance (142 mg).

Workup

  1. stirringthe mixture was stirred
  2. filtrationfiltered through Celite (registered trademark)
  3. concentrationThe filtrate was concentrated under reduced pressure, 1 mol/mL aqueous sodium hydroxide solution
  4. additionwas added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe desiccant was filtered off
  9. concentrationfollowed by concentration under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane only→hexane

Sources & evidence

ORD record
ord-e109fe4fd69e4d64b7d08863306fe8d5
Source dataset
uspto-grants-2015_05
Patent number
US09035059B2

Reaction notes

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