Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O-])(=O)C.[NH4+:5].[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([C:18]2O[C:20](/[CH:23]=[CH:24]/[C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]4)=[C:27]([O:37][CH3:38])[CH:26]=3)=[N:21][N:22]=2)[C:14](=[O:17])[CH:15]=[CH2:16])=[CH:9][CH:8]=1>C(O)(=O)C>[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:14](=[O:17])[CH2:15][CH2:16][N:5]3[C:20](/[CH:23]=[CH:24]/[C:25]4[CH:30]=[CH:29][C:28]([N:31]5[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]5)=[C:27]([O:37][CH3:38])[CH:26]=4)=[N:21][N:22]=[C:18]23)=[CH:9][CH:8]=1
Reactant: [NH4+]
Reactant: C=CC(=O)N(c1ccc(F)cc1)c1nnc(/C=C/c2ccc(-n3cnc(C)c3)c(OC)c2)o1
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Product: COc1cc(/C=C/c2nnc3n2CCC(=O)N3c2ccc(F)cc2)ccc1-n1cnc(C)c1
Temperature: 150 °C
Reaction time: 6 h
Yield: 4.6 %

Procedure:
Acetic acid (1 mL) and ammonium acetate (0.11 g) were added to N-(4-fluorophenyl)-N-{5-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-[1,3,4]oxadiazol-2-yl}acrylamide (22 mg), and the reaction solution was stirred at 150° C. for six hours. The reaction solution was left to cool to room temperature and then concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue, followed by extraction with chloroform. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system) to obtain 1 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: [CH3:1][C:2]1[O:7][CH2:6][N:5]([C:8]([CH3:15])([CH:10]([OH:14])[CH:11]([CH3:13])[CH3:12])[CH3:9])[C:4](=[O:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.CCOCC>ClCCl>[CH3:1][C:2]1[O:7][CH2:6][N:5]([C:8]([CH3:9])([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])[CH3:15])[C:4](=[O:16])[C:3]=1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C(O)C(C)C)CO1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C(=O)C(C)C)CO1
Reaction time: 5 h
Yield: 49.7 %

Procedure:
A solution of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2,4-dimethylpentan-3-ol (1.7 g) in dichloromethane was added to a stirred mixture of pyridinium chlorochromate (1.81 g) and powdered molecular sieve (4A) in dichloromethane at 20° C. After 5 hours, ether was added, the mixture filtered through hyflo and evaporated. The residue was purified by dry column chromatography on silica gel, eluting with dichloromethane/ethyl acetate to give 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2,4-dimethylpentan-3-one (Compound 1, 0.84 g) as a white solid, m-p. 98.6-101.6° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].O>CN(C)C=O>[C:23]([O:22][C:20](=[O:21])[CH2:19][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=1)([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: Cc1cccc(NC(=O)OC(C)(C)C)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cccc(N(CC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 101.9 %

Procedure:
To a solution of 2-(tert-butoxycarbonylamino)-6-methylpyridine (723 mg, 3.47 mmol) in N,N-dimethylformamide (11.5 ml) was added sodium hydride (mineral oil 55% dispersion) (0.18 g, 4.2 mmol) in portions under ice cooling. After stirring at room temperature for 30 minutes, tert-butyl bromoacetate (0.62 ml, 4.2 mmol) was added dropwise under ice cooling, followed by stirring at room temperature for 2 hours. After completion of the reaction, water was added to the reaction solution, followed by extraction with ethyl acetate. The separated organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=10:1→5:1 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (1.14 g) substantially quantitatively as a colorless liquid.
Reaction SMILES: [CH3:1][O:2]/[N:3]=[C:4](/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)\[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1.O[C:22]1[CH:27]=[CH:26][C:25]([CH:28]([C:34]#[C:35][CH3:36])[CH2:29][C:30]([O:32]C)=[O:31])=[CH:24][CH:23]=1>>[CH3:1][O:2]/[N:3]=[C:4](/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)\[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][C:22]2[CH:27]=[CH:26][C:25]([CH:28]([C:34]#[C:35][CH3:36])[CH2:29][C:30]([OH:32])=[O:31])=[CH:24][CH:23]=2)=[CH:9][CH:8]=1
Reactant: CO/N=C(\COc1ccc(CO)cc1)c1ccccc1
Reactant: CC#CC(CC(=O)OC)c1ccc(O)cc1
Product: CC#CC(CC(=O)O)c1ccc(OCc2ccc(OC/C(=N\OC)c3ccccc3)cc2)cc1
Yield: 20.59 %

Procedure:
Compound 85 was synthesized from (4-{[(2Z)-2-(methoxyimino)-2-phenylethyl]oxy}phenyl)methanol (0.2 g, 0.74 mmol) and methyl 3-(4-hydroxyphenyl)hex-4-ynoate (0.16 g, 0.74 mmol) by following the procedure described in scheme 28 (0.03 g, yield: 20.59%); Purity: 98.37%.
Reaction SMILES: [CH:1]1([NH:7][C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-])=O)[CH:13]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C=O)C>C(O)C.[Ni]>[NH2:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][NH:10][C:8]([NH:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:9]
Reactant: O=C(NCc1cccc([N+](=O)[O-])c1)NC1CCCCC1
Agent: [Ni]
Solvent: CCO
Solvent: CN(C)C=O
Product: Nc1cccc(CNC(=O)NC2CCCCC2)c1
Reaction time: 2 h
Yield: 84.1 %

Procedure:
1-Cyclohexyl-3-(3-nitro-benzyl)-urea (4 g) was suspended in ethanol (70 ml) and Raney nickel (2 g) was added. Under stirring aqueous hydrazine solution (2.5 ml, 80%) was added. DMF was added (50 ml) and the reaction mixture was stirred for additional 2 h and filtered. The solution was evaporated i.v. affording the title compound (3 g, Rf=0.43 DCM/ethanol 19:1).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[OH:9].Cl[CH2:11][C:12](Cl)=[O:13].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:12](=[O:13])[CH2:11][O:9][C:3]=2[CH:4]=1
Reactant: Nc1ccc(Cl)cc1O
Reactant: O=C(Cl)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1COc2cc(Cl)ccc2N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 2-amino-5-chloro-phenol (27) (2.0 g, 14 mmol, 1 equiv) in 30 ml of THF, chloroacetyl chloride (1.26 ml, 16.8 mmol, 1.2 equiv), and saturated aqueous NaHCO3 50 mL was stirred at RT for 2 hrs and then heated at 80° C. overnight. The reaction mixture was diluted with EtOAc, and washed with water. Purification of the crude product by flash chromatography provided 7-chloro-4H-benzo[1,4]oxazin-3-one (28): LCMS Retention time: 1.48 min.; LCMS observed (M+H)+: 184.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].N1C=CN=C1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Si:17]([O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[NH2:1])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]
Reactant: Nc1ccc([N+](=O)[O-])cc1O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1cc([N+](=O)[O-])ccc1N
Temperature: 23 °C
Reaction time: 48 h
Yield: 97.6 %

Procedure:
To a solution of 2-amino-5-nitrophenol (1 g, 6.49 mmol) and imidazole (0.88 g, 12.3 mmol) in DMF (15 mL), tert-butyldimethylsilyl chloride (11.2 mL, 64.9 mmol) was added. The resulting mixture was allowed to stir at 23° C. for 48 hours. The reaction mixture was partitioned between 0.1% HCl and ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4 and filtered. Removal of solvent at reduced pressure and chromatography of the resulting oil on silica gel (hexane:ethyl acetate; 5:1) gave the titled compound (1.7 g, 98%). 1H NMR (CDCl3): δ 7.78 (dd, 1H, J=6.7 Hz and J=2.7 Hz), 7.61 (d, 1H, J=2.7 Hz), 6.7 (d, 1H, J=8.8 Hz), 1.0 (s, 9H), 0.28 (s, 6H).
Reaction SMILES: [CH:1]([O:4][C:5]1[N:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH:7]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]([F:30])([F:29])[F:28])[C:8]([C:16]([O:18]CC)=O)=[C:9]([CH3:15])[NH:10]2)([CH3:3])[CH3:2].[H-].[Na+].[N:33]1C=NC=N[CH:34]=1>CN(C)C=O>[CH:1]([O:4][C:5]1[C:6]2[CH:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:29])([F:28])[F:30])[C:8]3[C:16](=[O:18])[NH:33][CH:34]=[CH:15][C:9]=3[NH:10][C:11]=2[CH:12]=[CH:13][N:14]=1)([CH3:2])[CH3:3]
Reactant: c1ncncn1
Reactant: CCOC(=O)C1=C(C)Nc2ccnc(OC(C)C)c2C1c1ccccc1C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)Oc1nccc2c1C(c1ccccc1C(F)(F)F)c1c(cc[nH]c1=O)N2
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of 11.3 g (27 mMole) ethyl (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoro methylphenyl)-1,6-naphthyridine-3-carboxylate in 200 ml dimethylformamide is added dropwise, under an atmosphere of nitrogen, to a suspension of 1.0 g (33 mMole) sodium hydride (80% in oil) in 20 ml dry dimethylformamide. After cessation of the gas evolution, the reaction mixture is stirred for 10 minutes at ambient temperature and subsequently 2.5 g (31 mMole) s-triazine in 20 ml dimethylformamide are added dropwise thereto. The reaction mixture is stirred for 16 hours at 105° C. and, after cooling, evaporated in a vacuum. The residue is chromatographed on silica gel with dichloromethane/methanol (95:5 v/v) and the fraction with an Rf of 0.6 is isolated and recrystallized from ethyl acetate/ethanol (9:1 v/v). There is obtained (±)-1,2,5,10-tetrahydro-9-isopropoxy-1-oxo-10-(2-trifluoromethylphenyl)-pyrido[4,3-b][1,6]naphthyridine in the form of colorless crystals; mp 315° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[NH:10][N:9]=[C:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19]>C(N(C(C)C)CC)(C)C>[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH:19][C:4]1[C:5]2[NH:10][N:9]=[C:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([Cl:1])[N:3]=1
Reactant: CC(C)c1n[nH]c2c(Cl)nc(Cl)nc12
Reactant: Nc1cccc(Cl)c1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)c1n[nH]c2c(Nc3cccc(Cl)c3)nc(Cl)nc12
Yield: 16 %

Procedure:
5,7-Dichloro-3-isopropylpyrazolo[4,3-d]pyrimidine (90 mg), 1.2 mL of 3-chloroaniline and 250 μL of diisopropyl ethylamine were stirred at 60° C. for 24 hours. The reaction mixture was evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with the following solvent system: CHCl3/heptane (100/17), to give 7-(3-chloroanilino)-5-chloro-3-isopropylpyrazolo[4,3-d]pyrimidine, yield 16%, mp=257-259° C. MS (ES+): 322.3 (100%, M+H+), 324.3 (64%, M+H+). 1H NMR (CDCl3; 300 MHz): 1.54 d (6H, J=7.1 Hz); 3.60 sept (1H, J=7.1 Hz), 7.16 d (1H), 7.34 t (1H), 7.88 d (1H), 8.10 s (1H).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[O:12][CH2:13][C:14]([CH3:16])=[CH2:15])[CH3:2].Cl[C:18]1[N:19]=[N:20][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:22][CH:23]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[Cl:11][C:9]1[CH:8]=[CH:7][C:6]([O:12][CH2:13][C:14]([CH3:16])=[CH2:15])=[C:5]([CH:10]=1)[CH2:4][N:3]([C:18]1[N:19]=[N:20][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:22][CH:23]=1)[CH2:1][CH3:2]
Reactant: C=C(C)COc1ccc(Cl)cc1CNCC
Reactant: NS(=O)(=O)c1ccc(Cl)nn1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C=C(C)COc1ccc(Cl)cc1CN(CC)c1ccc(S(N)(=O)=O)nn1
Temperature: 130 °C
Reaction time: 16 h

Procedure:
A mixture of N-ethyl-5-chloro-2-(2-methylprop-2-en-1-yloxy)benzylamine (2.76 g, 10 mmol), 3-chloro-pyridazine-6-sulphonamide [Archiv der Pharmazie (1966) 299, 646-650 and EP patent no 96,004] (1.5 g, 7.8 mmol) and ethyl di-isopropylamine (10 ml, 57 mM) in DMF (50 ml) was stirred at 130° C. for 16 hours under a reflux condenser. The solvent was evaporated at reduced pressure and the residue partitioned between dichloromethane (100 ml) and water (100 ml). The organic layer was separated, dried over anhydrous magnesium sulphate, filtered and evaporated to give a brown gum (2.5 g). The brown gum was purified by chromatography on silica, eluting with a gradient of 0→20% ethyl acetate in dichloromethane to give the title compound as a yellow solid (600 mg).
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:14](O)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH2:24][C:25]1[N:30]=[C:29]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:28]=[CH:27][CH:26]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>CN(C=O)C>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[C:14]([NH:24][C:25]3[N:30]=[C:29]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:28]=[CH:27][CH:26]=3)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1
Reactant: O=C(O)C(OC1CCOCC1)c1ccc(S(=O)(=O)C2CC2)cc1
Reactant: CCOC(=O)Cc1cccc(N)n1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CCOC(=O)Cc1cccc(NC(=O)C(OC2CCOCC2)c2ccc(S(=O)(=O)C3CC3)cc2)n1
Yield: 46.2 %

Procedure:
The compound of example A9 was obtained by similar method described in example A1 using 2-(4-cyclopropanesulfonyl-phenyl)-2-[(tetrahydro-pyran-4-yloxy)]-acetic acid (Preparation 4; 0.990 g, 2.91 mmol), ethyl 2-(6-amino-2-pyridyl)acetate (0.35 g, 1.94 mmol), HOBt (0.65 g, 4.81 mmol), and EDCl (0.92 g, 4.81 mmol), N-methyl morpholine (0.64 mL, 5.83 mmol) in DMF (25 mL) to provide the title compound (0.45 g).
Reaction SMILES: CS(O[CH2:6][CH2:7][NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)(=O)=O.[NH3:18]>CN(C)C=O>[NH2:18][CH2:6][CH2:7][NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1
Reactant: CS(=O)(=O)OCCNC(=O)c1ccc(Cl)cc1
Reactant: N
Solvent: CN(C)C=O
Product: NCCNC(=O)c1ccc(Cl)cc1
Reaction time: 2 h

Procedure:
The N-(2-methylsulfonyloxyethyl)-4-chlorobenzamide obtained is dissolved in 5 ml of dimethylformamide and added dropwise at room temperature to a solution of ammonia in dimethylformamide. After stirring for 2 hours, the mixture is worked-up and there is obtained N-(2-aminoethyl)-4-chlorobenzamide which is identical with the product obtained in Example 1.
Reaction SMILES: C[Al](C)C.[O:5]1[CH:9]=[CH:8][CH:7]=[C:6]1[CH2:10][S:11][CH2:12][CH2:13][C:14]([O:16]C)=O.[NH2:18][CH2:19][C:20]([N:22]1[CH2:28][C:27]2[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=2[O:25][C:24]2[CH:33]=[CH:34][C:35]([Cl:37])=[CH:36][C:23]1=2)=[O:21].CO>C1(C)C=CC=CC=1>[Cl:37][C:35]1[CH:34]=[CH:33][C:24]2[O:25][C:26]3[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=3[CH2:28][N:22]([C:20](=[O:21])[CH2:19][NH:18][C:14](=[O:16])[CH2:13][CH2:12][S:11][CH2:10][C:6]3[O:5][CH:9]=[CH:8][CH:7]=3)[C:23]=2[CH:36]=1
Reactant: NCC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Reactant: COC(=O)CCSCc1ccco1
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Solvent: CO
Product: O=C(CCSCc1ccco1)NCC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Reaction time: 5 h

Procedure:
Trimethylaluminum (2.0M in toluene; 4.6 mL) was added dropwise via syringe to a stirred solution of methyl 3-[(2-furanylmethyl)thio]propanoate (0.75 gram) and 10-(aminoacetyl)-8-chloro-10,11-dihydrodibenz-[b,f][1,4]oxazepine (1.00 gram) in toluene (30 mL) at room temperature under nitrogen, and the reaction was stirred for 5 hours. Methanol (14 mL) was then added, and the reaction was stirred at room temperature overnight. The reaction was evaporated in vacuo, and the resulting orange residue was partitioned between chloroform (50 mL) and 1N NaOH (50 mL). The layers were separated and the aqueous layer was extracted with chloroform (50 mL). The combined chloroform extracts were washed with 1N NaOH (50 mL), 1N HCl (2×50 mL), and brine (50 mL), dried over MgSO4, and evaporated in vacuo. The crude product was purified by flash chromatography through silica gel 60 (350 mL) using 3:1 chloroform:ethyl acetate followed by recrystallization from cyclohexane/ethyl acetate. The yield of the title compound was 0.63 gram (40%) in the form of a tan solid. Analysis calculated for C23H21ClN2O4S: C, 60.46; H, 4.63;N, 6.13; Cl, 7.67; S, 7.02. Found: C, 60.16; H, 4.62;N, 6.05; Cl, 8.06; S, 7.02. DSC: 90°-95° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]#[C:12][C:13]2[N:18]=[C:17]([C:19]([OH:21])=O)[CH:16]=[CH:15][CH:14]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:55][O:56][C:57]([C:59]1[C:67]2[N:66]=[C:65]([NH2:68])[NH:64][C:63]=2[CH:62]=[CH:61][CH:60]=1)=[O:58]>CN(C=O)C>[CH3:55][O:56][C:57]([C:59]1[C:67]2[N:66]=[C:65]([NH:68][C:19]([C:17]3[CH:16]=[CH:15][CH:14]=[C:13]([C:12]#[C:11][C:7]4[CH:8]=[CH:9][CH:10]=[C:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH:6]=4)[N:18]=3)=[O:21])[NH:64][C:63]=2[CH:62]=[CH:61][CH:60]=1)=[O:58]
Reactant: CS(=O)(=O)c1cccc(C#Cc2cccc(C(=O)O)n2)c1
Reactant: COC(=O)c1cccc2[nH]c(N)nc12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cccc2[nH]c(NC(=O)c3cccc(C#Cc4cccc(S(C)(=O)=O)c4)n3)nc12
Reaction time: 0.08 h
Yield: 66.5 %

Procedure:
To a solution of 136 mg (0.45 mmol) of 6-(3-methanesulfonyl-phenylethynyl)-pyridine-2-carboxylic acid in DMF (2 mL) was added 210 mg (0.55 mmol) of HBTU (210 mg) and DIEA (0.2 mL). The mixture was stirred for 5 min then 96 mg (0.5 mmol) of 2-amino-1H-benzoimidazole-4-carboxylic acid methyl ester (Intermediate A) was added. The reaction mixture was stirred at 30° C. for 30 min. After usual workup as described in general procedure A, 142 mg (60%) of 2-{[6-(3-Methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid methyl ester was obtained after column chromatography eluting with DCM/EtOAc (v/v=1:1) then EtOAc. LCMS: 475 (M+1)+. This ester was hydrolyzed as described in general procedure B to provide 135 mg (100%) of 2-{[6-(3-methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid. LCMS: 461 (M+1)+.
Reaction SMILES: [C:1]1([C:7]23[CH2:15][CH2:14][CH2:13][CH:12]2[CH2:11][NH:10][CH2:9][CH2:8]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:16]1([C:19](Cl)=[O:20])[CH2:18][CH2:17]1>>[C:1]1([C:7]23[CH2:15][CH2:14][CH2:13][CH:12]2[CH2:11][N:10]([C:19]([CH:16]2[CH2:18][CH2:17]2)=[O:20])[CH2:9][CH2:8]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(C23CCCC2CNCC3)cc1
Reactant: O=C(Cl)C1CC1
Product: O=C(C1CC1)N1CCC2(c3ccccc3)CCCC2C1

Procedure:
Following the procedure outlined in Example 28, 4a-phenyl-2,3,4,4a,5,6,7,7a-octahydro-1H-2-pyrindine was acylated with cyclopropanecarboxylic acid chloride to provide 4a-phenyl-2-cyclopropanecarbonyl-2,3,4,4a,5,6,7,7a-octahydro-1H-2-pyrindine. Reduction of the acylated pyrindine intermediate by reaction with lithium aluminium hydride afforded the corresponding 2-alkyl pyrindine, which when reacted with hydrobromic acid provided 4a-phenyl-2-cyclopropylmethyl-2,3,4,4a,5,6,7,7a-octahydro-1H-2-pyrindinium bromide. M.P. 240°-241° C.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]([CH:15]1[CH2:20][CH2:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:23][CH:22]=2)=[CH:17][CH2:16]1)[CH2:13][CH3:14]>CCOCC>[CH2:27]([C:24]1[CH:25]=[CH:26][C:21]([C@H:18]2[CH2:19][CH2:20][C@H:15]([CH2:12][CH2:13][CH3:14])[CH2:16][C:17]2=[O:9])=[CH:22][CH:23]=1)[CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CCCCCc1ccc(C2=CCC(CCC)CC2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CCOCC
Product: CCCCCc1ccc([C@H]2CC[C@H](CCC)CC2=O)cc1
Reaction time: 16 h

Procedure:
15 g of m-chloroperbenzoic acid are added at 0° to a solution of 20 g of p-(4-n-propylcyclohex-1-en-1-yl)-n-pentylbenzene (German Offenlegungsschrift 3,006,666) in 100 ml of ether, and the mixture is stirred for 16 hours. The reaction mixture is extracted several times with 10% sodium hydroxide solution, and the organic phase is dried with sodium sulfate. 40 ml of BF3 /ether complex (50% of BF3) are added to the resulting solution of epoxide, and the mixture is stirred for 5 minutes and is then poured onto ice. Working up in the customary manner gives trans-2-(p-n-pentylphenyl)-5-n-propylcyclohexanone. b.p. (0.1 mm Hg) 140°, c.p. -10°.
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].[CH3:6][CH:7]([O:9][C:10]1[C:15]2[CH2:16][CH2:17][CH2:18][C:19](=[O:21])[NH:20][C:14]=2[CH:13]=[CH:12][CH:11]=1)[CH3:8].C(=O)(O)[O-].[Na+]>FC(F)(F)C(OC(=O)C(F)(F)F)=O>[N+:1]([C:11]1[CH:12]=[CH:13][C:14]2[NH:20][C:19](=[O:21])[CH2:18][CH2:17][CH2:16][C:15]=2[C:10]=1[O:9][CH:7]([CH3:8])[CH3:6])([O-:4])=[O:2]
Reactant: CC(C)Oc1cccc2c1CCCC(=O)N2
Reactant: O=[N+]([O-])[O-]
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CC(C)Oc1c([N+](=O)[O-])ccc2c1CCCC(=O)N2
Temperature: -5 °C
Reaction time: 0.08 h
Yield: 28.7 %

Procedure:
750 mg of potassium nitrate are added, in portions, to a solution of 1.3 g of 6-(propan-2-yloxy)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in 13 ml of trifluoroacetic anhydride brought back to −5° C. The reaction medium is stirred for 5 minutes at −5° C. and then brought back to pH 5 by adding a saturated aqueous sodium bicarbonate solution. The mixture is extracted with ethyl acetate and the organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification is carried out by flash chromatography on silica gel (40-63 μm), elution being carried out with a mixture of heptane and of ethyl acetate (80/20 to 50/50). 450 mg of 7-nitro-6-(propan-2-yloxy)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one are obtained in the form of a beige solid. 91 mg of sodium hydride at 50% are added to a solution of 445 mg of 7-nitro-6-(propan-2-yloxy)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in 10 ml of DMF. The reaction medium is stirred for 10 minutes at ambient temperature and then 263 mg of iodomethane are added. The reaction medium is stirred for 1 hour at ambient temperature, poured into ice-cold water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and evaporated under reduced pressure, so as to give 417 mg of 1-methyl-7-nitro-6-(propan-2-yloxy)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in the form of a yellow gum.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[F:14][C:15]([F:31])([F:30])[C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:19](=O)[CH2:20]Br>>[F:14][C:15]([F:30])([F:31])[C:16]1[CH:17]=[C:18]([C:19]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[O:3][CH:20]=2)[CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1
Reactant: O=C(CBr)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: COC(=O)c1ccc(C(N)=O)cc1
Product: COC(=O)c1ccc(-c2nc(-c3cc(C(F)(F)F)cc(C(F)(F)F)c3)co2)cc1
Yield: 24 %

Procedure:
In the same manner as in Example 1, methyl 4-carbamoylbenzoate was reacted with 3,5-bis(trifluoromethyl)phenacyl bromide to obtain methyl 4-[4-[3,5-bis(trifluoromethyl)phenyl]-2-oxazolyl]benzoate. The product was. recrystallized from ethanol., Yield: 24%. Pale yellow prisms. Melting Point: 180 to 181° C.