2,3-dihydro-1H-indene-1-carboxamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 150 ml of diborane (1M in THF) in 250 ml of dry THF. Ten g of 1-indane carboxamide is slowly added. Reaction mixture is stirred at reflux for three hours, cooled to room temperature, and worked up by slowly adding 150 ml of 1N HCl. THF is distilled off under reduced pressure, the aqueous solution is brought to pH~13 by addition of NaOH. It is extracted with ethyl acetate (2×300 ml). The organic extract is washed with water (1×100 ml), dried over MgSO4, filtered, and evaporated to dryness affording 6.5 g (71%) of 1-indanylmethylamine. It was used as is in the next reaction. Reaction mixture at reflux for three hours THF is distilled off under reduced pressure the aqueous solution is brought to pH~13 by addition of NaOH It is extracted with ethyl acetate (2×300 ml) The organic extract is washed with water (1×100 ml) dried over MgSO4 filtered evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 150 ml of diborane (1M in THF) in 250 ml of dry THF. Ten g of 1-indane carboxamide is slowly added. Reaction mixture is stirred at reflux for three hours, cooled to room temperature, and worked up by slowly adding 150 ml of 1N HCl. THF is distilled off under reduced pressure, the aqueous solution is brought to pH~13 by addition of NaOH. It is extracted with ethyl acetate (2×300 ml). The organic extract is washed with water (1×100 ml), dried over MgSO4, filtered, and evaporated to dryness affording 6.5 g (71%) of 1-indanylmethylamine. It was used as is in the next reaction. Reaction mixture at reflux for three hours THF is distilled off under reduced pressure the aqueous solution is brought to pH~13 by addition of NaOH It is extracted with ethyl acetate (2×300 ml) The organic extract is washed with water (1×100 ml) dried over MgSO4 filtered evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared using the procedure as described in Example 80 substituting 2-chloro-3-trifluoromethylphenylhydrazine hydrochloride for phenylhydrazine hydrochloride and substituting N-formyl-2,3-dihydro-1H-indene-1-carboxamide (prepared using the procedure as described in Example 76A, substituting from indan-1-carboxamide [Seidl Tetrahedron 1964, 20, 633] for 2-o-tolylacetamide) for N-formylphenylacetamide. The residue was purified by flash chromatography (40% ethyl acetate/hexanes) to provide the title compound. MS (ESI) m/e: 364 (M+H)+; 1H NMR (DMSO-d6) δ 2.05-2.45 (m, 2H), 2.8-3.05 (m, 2H), 4.29-4.35 (t, 1H), 6.95-7.05 (bs, 1H), 7.03-7.1 (t, 1H), 7.1-7.21 (t, 1H), 7.2-7.3 (d, 1H), 7.78-7.82 (t, 2H), 8.0-8.01 (bs, 0.5H), 8.18 (s, 1H), 8.22 (bs, 0.5H); Anal. calcd. for C, 59.43; H, 3.60; N, 11.55. Found C, 59.20; H, 3.34; N, 11.48 The title compound was prepared prepared The residue was purified by flash chromatography (40% ethyl acetate/hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As depicted in Scheme 2, the reaction of an appropriately substituted indanyl amine, for example 4-fluoroindanylamine (known compound, U.S. Pat. No. 5,486,541) with 2-chloroethyl isocyanate (SM4) under basic conditions, in an appropriate solvent yielded the corresponding indanyl carboxamide intermediate (a), for example, [(2-chloroethyl)amino]-N-(4-fluoroindanyl)carboxamide. Intermediate (a) was heated under basic conditions in an appropriate solvent to yield the appropriate indanyl 1,3-oxazolidine, a compound of formula I and an intermediate (b), for example, 2-[aza(4-fluoroindanyl)methylene]-1,3-oxazolidine, described in detail in Example 2, Step B, as set forth below. Compound (b) was reacted with an isothiocyanate, for example, methyl isothiocyanate, under basic conditions yielding the corresponding amino methane-1-thione, for example, 2-[aza(4-fluoroindanyl)methylene](1,3-oxazolidin-3-yl)(methylamino)methane-1-thione, a compound of formula I, described in detail in Example 2, Step C, as set forth below.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 150 ml of diborane (1M in THF) in 250 ml of dry THF. Ten g of 1-indane carboxamide is slowly added. Reaction mixture is stirred at reflux for three hours, cooled to room temperature, and worked up by slowly adding 150 ml of 1N HCl. THF is distilled off under reduced pressure, the aqueous solution is brought to pH~13 by addition of NaOH. It is extracted with ethyl acetate (2×300 ml). The organic extract is washed with water (1×100 ml), dried over MgSO4, filtered, and evaporated to dryness affording 6.5 g (71%) of 1-indanylmethylamine. It was used as is in the next reaction. Reaction mixture at reflux for three hours THF is distilled off under reduced pressure the aqueous solution is brought to pH~13 by addition of NaOH It is extracted with ethyl acetate (2×300 ml) The organic extract is washed with water (1×100 ml) dried over MgSO4 filtered evaporated to dryness