Methanol → 2-Cyclobutoxy-N-(2-methanesulfonylaminocarbonyl-indan-2-yl)-3-methyl-benzamide

HRID 1047827Notes

Reaction equation

HRID 1047827 reaction equation
[CH:1]1([O:5][C:6]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:7]=2[C:8]([NH:10][C:11]2([C:20](O)=[O:21])[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12]2)=[O:9])[CH2:4][CH2:3][CH2:2]1.[CH3:28][S:29]([NH2:32])(=[O:31])=[O:30].Cl.CN(C)CCCN=C=NCC.CO>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:1]1([O:5][C:6]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:7]=2[C:8]([NH:10][C:11]2([C:20]([NH:32][S:29]([CH3:28])(=[O:31])=[O:30])=[O:21])[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12]2)=[O:9])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 251602822-(2-Cyclobutoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid

Product 1

HCID 251613042-Cyclobutoxy-N-(2-methanesulfonylaminocarbonyl-indan-2-yl)-3-methyl-benzamideYield 87.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A 30 mL vial is charged with 2-[(2-cyclobutoxy-3-methyl-benzoyl)-amino]-indan-2-carboxylic acid (245 mg, 0.67 mmol) and dry DCM (5.0 mL). A stirring bar is added and stirring is initiated. The methanesulfonamide (89 mg, 0.936 mmol) is added. To the resultant suspension, (N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (120 mg, 0.624 mmol) and 4-dimethylaminopyridine (76 mg, 0.62 mmol) are added. After 6 days, tlc analysis (silica, 10% MeOH in DCM) indicates that the starting acid is consumed. The reaction mixture is diluted with EtOAc (50 mL), transferred to a separatory funnel and washed with dilute aqueous HCl (3 N, 3×20 mL) and brine, dried over MgSO4, filtered and evaporated by pumping to constant weight gives 0.26 g of amorphous white foam. This material is dissolved in DCM (5 mL) and applied to a 12 g column (silica) on an ISCO Companion. The column is eluted with 1% iPrOH in DCM for 3 column volumes followed by a linear gradient to 30% iPrOH in DCM over 15 column volumes. 12 mL fractions of UV active eluent are collected. Fractions 4 through 9 are combined and evaporated to a constant weight to give 0.2 g of white solid.

Workup

  1. additionA stirring bar is added
  2. customis consumed
  3. additionThe reaction mixture is diluted with EtOAc (50 mL)
  4. customtransferred to a separatory funnel
  5. washwashed with dilute aqueous HCl (3 N, 3×20 mL) and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-7e93117f41ba47e29fbd049058b3f3d0
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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