Lithium Hydroxide → 2-[4-Methoxy-3-(2-m-tolyl-ethylsulfanyl)-benzoylamino]-indane-2-carboxylic acid

HRID 2405247Notes

Reaction equation

HRID 2405247 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[S:12][CH2:13][CH2:14][C:15]1[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.C[O:48][C:49]([C:51]1([NH2:60])[CH2:59][C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:52]1)=[O:50].[Cl-].[Li+].[OH-].[Li+]>CN(C=O)C.C1COCC1.O.CC(=O)OCC>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:60][C:51]2([C:49]([OH:50])=[O:48])[CH2:52][C:53]3[C:58](=[CH:57][CH:56]=[CH:55][CH:54]=3)[CH2:59]2)=[O:9])=[CH:5][C:4]=1[S:12][CH2:13][CH2:14][C:15]1[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=1

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 433294Lithium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45074056methyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate hydrochlorideHCID 670766864-Methoxy-3-(2-m-tolyl-ethylsulfanyl)-benzoic acid

Product 1

HCID 444785022-[4-Methoxy-3-(2-m-tolyl-ethylsulfanyl)-benzoylamino]-indane-2-carboxylic acidYield 20.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

700 mg of the crude compound of step 2 were dissolved in 5 ml of DMF and 598 mg (4.63 mmol) of EDIA and 968 mg (2.55 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate were added. Then a solution of 527 mg (2.32 mmol) of 2-amino-indane-2-carboxylic acid methyl ester hydrochloride in 5 ml of DMF was added. After stirring overnight, EA and an aqueous solution of lithium chloride (4%) were added, the organic phase was separated, washed once with a solution of lithium chloride and twice with a solution of sodium hydrogencarbonate, dried and evaporated. The solid residue was dissolved in 10 ml of a 9:1 mixture of THF and water, and 131 mg (5.47 mmol) of lithium hydroxide were added. After stirring overnight, the mixture was evaporated to dryness. The residue was purified by preparative RP HPLC (water/ACN gradient) to give 222 mg of the title compound.

Workup

  1. customthe organic phase was separated
  2. washwashed once with a solution of lithium chloride and twice with a solution of sodium hydrogencarbonate
  3. customdried
  4. customevaporated
  5. additionwere added
  6. stirringAfter stirring overnight
  7. customthe mixture was evaporated to dryness
  8. customThe residue was purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-5ffb27491cf04f55bb146007c0482bdd
Source dataset
uspto-grants-2014_08
Patent number
US08802720B2

Reaction notes

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