Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[O:9])=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:27][C:28]([O:30][CH3:31])=[O:29]>O1CCCC1.C1(C)C=CC=CC=1>[CH3:17][O:16][C:13]1[CH:12]=[CH:11][C:10]([C:8](=[O:9])[CH:7]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:15][CH:14]=1
Reactant: COC(=O)CBr
Reactant: COc1ccc(C(=O)Cc2ccncc2)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COC(=O)CC(C(=O)c1ccc(OC)cc1)c1ccncc1
Reaction time: 0.5 h

Procedure:
Under an argon, 2-(4-pyridyl)-4′-methoxyacetophenone (J. Am. Chem. Soc., 112, 2163-3168, 1990: Dimitrios Stefanidis and John W. Bunting; 9.6 g, 42.3 mmol) was suspended in tetrahydrofuran (200 ml), and under ice cooling, lithium diisopropylamide (2.0 M solution; 25 ml, 50.0 mmol) was added. At the same temperature, the mixture was stirred for 30 minutes. Methyl bromoacetate (6.0 ml, 63.4 mmol) was then added dropwise, and the mixture was stirred under ice cooling for 1 hour and then at room temperature for 2 hours. The reaction mixture was diluted with toluene. The mixture was washed successively with 2 N hydrochloric acid, water and a brine, and was then dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was separated and purified by chromatography on a silica gel column [silica gel: 100 g, hexane/ethyl acetate (1/2)], whereby the title compound (10.63 g, 84.1%) was obtained as a brown oil.
Reaction SMILES: [CH:1]1([CH2:4][NH2:5])[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl.[F:14][C:15]([F:49])([F:48])[C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[N:19]=[C:18]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38]3[CH:39]=[C:40]([S:44](Cl)(=[O:46])=[O:45])[CH:41]=[CH:42][CH:43]=3)[CH:33]=2)[N:17]=1>C1COCC1>[CH:1]1([CH2:4][NH:5][S:44]([C:40]2[CH:41]=[CH:42][CH:43]=[C:38]([C:34]3[CH:33]=[C:32]([C:18]4[N:17]=[C:16]([C:15]([F:14])([F:48])[F:49])[CH:21]=[C:20]([C:22]5[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=5)[N:19]=4)[CH:37]=[CH:36][N:35]=3)[CH:39]=2)(=[O:45])=[O:46])[CH2:3][CH2:2]1
Reactant: O=S(=O)(Cl)c1cccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)ccn2)c1
Reactant: NCC1CC1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=S(=O)(NCC1CC1)c1cccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)ccn2)c1
Temperature: 0 °C
Yield: 91.8 %

Procedure:
To a cooled (ice-water bath) and stirred mixture of cyclopropylmethylamine (0.21 g, 2.96 mmol), triethylamine (0.28 ml, 2.0 mmol) and THF (4 ml) was added drop wise a solution of 3-{4-[4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl]-pyridin-2-yl}-benzenesulfonyl chloride hydrochloride (example I.1) (0.56 g, 0.96 mmol) in THF (6 ml). The mixture was allowed to stir at room temperature for 16 h. Purification of the reaction mixture by flash chromatography on silica gel (ethyl acetate/heptane) and crystallization (dichloromethane/MeOH/hexane) yielded the title compound as a white solid (0.51 g, 97%). MS (ISP) 578.6 [(M+H)+]; mp 133.5° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([C@@H:11]([NH:14]S(C(C)(C)C)=O)[CH2:12][CH3:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[ClH:21].O1CCOCC1>CO>[ClH:21].[CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([C@@H:11]([NH2:14])[CH2:12][CH3:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CC[C@H](NS(=O)C(C)(C)C)c1ccc(S(C)(=O)=O)nc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CC[C@H](N)c1ccc(S(C)(=O)=O)nc1
Reaction time: 1 h

Procedure:
To a solution of 2-methyl-propane-2-sulfinic acid [(S)-1-(6-methanesulfonyl-pyridin-3-yl)-propyl]-amide (50.0 g, 157.0 mmol) in methanol (500 mL) was added a 4 N solution of HCl in dioxane (40.0 mL, 160.0 mmol). After 1 hour, the mixture was concentrated to near dryness (about 40 mL) and the resulting mixture was diluted with ether (500 mL) to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[N:26]([CH3:29])=[C:27]=[O:28]>C(Cl)(Cl)Cl>[CH3:29][NH:26][C:27]([N:15]1[CH2:16][CH2:17][CH:12]([C:6]2([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)[C:5]3[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][C:7]2=[O:11])[CH2:13][CH2:14]1)=[O:28]
Reactant: CN=C=O
Reactant: O=C1Nc2cc(Cl)ccc2C1(Cc1cccc(Cl)c1)C1CCNCC1
Solvent: ClC(Cl)Cl
Product: CNC(=O)N1CCC(C2(Cc3cccc(Cl)c3)C(=O)Nc3cc(Cl)ccc32)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-4-yl-1,3-dihydro-indol-2-one (30 mg, 0.08 mmol) (from Example 15a supra) in chloroform (2 mL) was added isocyanatomethane (5.4 mg, 0.096 mmol) (Chem. Service). The mixture was stirred at room temperature for 16 hours. The solvent was evaporated and resulting material was recrystallized from dichloromethane-hexanes to give rac-4-[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-piperidine-1-carboxylic acid methylamide as a white solid. (Yield 5 mg, 14.5%).
Reaction SMILES: C([Li])CCC.[CH2:6]([C@H:13]1[CH2:17][O:16][C:15](=[O:18])[NH:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:19][C:20]1[CH:30]=[CH:29][C:23]([O:24][CH2:25][C:26](Cl)=[O:27])=[CH:22][CH:21]=1>CCCCCC.O1CCCC1>[CH2:6]([C@H:13]1[CH2:17][O:16][C:15](=[O:18])[N:14]1[C:26](=[O:27])[CH2:25][O:24][C:23]1[CH:29]=[CH:30][C:20]([CH3:19])=[CH:21][CH:22]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: Cc1ccc(OCC(=O)Cl)cc1
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1ccc(OCC(=O)N2C(=O)OC[C@@H]2Cc2ccccc2)cc1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Oxalyl chloride (8.83 ml) and N,N-dimethylformamide (3 drops) were added at room temperature to a solution of 4-methylphenoxyacetic acid (6.73 g) in dichloromethane (70 ml), and the reaction mixture was stirred for 1.5 hours. The reaction solution was concentrated under reduced pressure, then the resulting acidic gas was removed as the toluene azeotrope, and the product was dried under reduced pressure to give 4-methylphenoxyacetyl chloride. A 1.61N solution of n-butyl lithium in hexane (25.2 ml) was added dropwise at −78° C. to a solution of (S)-4-benzyl-2-oxazolidinone (7.08 g) in tetrahydrofuran (70-ml), and after the completion of the dropwise addition, the reaction mixture was stirred at −78° C. for 30 minutes. To this resulting solution was added at −78° C. a solution of 4-methylphenoxyacetyl chloride obtained above in tetrahydrofuran (70 ml) followed by stirring at 0° C. for 1 hour. The resulting reaction mixture was partitioned between ethyl acetate and water, and the ethyl acetate layer was washed successively with a 1N aqueous solution of hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by chromatography on a silica gel column (eluant; hexane/ethyl acetate =3/1˜1/1) to afford the target compound (9.00 g) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2.[CH2:22]([C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)[CH3:23].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:22][CH3:23])=[CH:25][CH:26]=1)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2
Reactant: CCOC(=O)C1=Cc2cc(Cl)c(F)cc2OC1C(F)(F)F
Reactant: CCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C1=Cc2cc(Cl)c(Oc3ccc(CC)cc3)cc2OC1C(F)(F)F
Temperature: 100 °C

Procedure:
To 4.05 g (12.5 mmole) of ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate in 30 mL of DMF was added 1.86 g (15.2 mmole) of 4-ethylphenol and 2.42 g (17.5 mmole) of potassium carbonate. The stirred mixture was heated to 100° C. for 8 h, allowed to cool and treated with 100 mL of water. The mixture was extracted three times with diethyl ether, the combined filtrates filtered through 30 g of silica and the filtrates concd in vacuo to afford a crude product. Recrystallization from methanol-water afforded 4.43 g (83%) of a yellow, crystalline solid: mp 109-110° C.; 1H NMR (d6-acetone/400 MHz) 1.22 (t, 3H, J=7.5 Hz), 1.30 (t, 3H, J=7.1 Hz), 2.66 (q, 2H, J=7.6 Hz), 4.28 (m, 2H), 5.81 (q, 1H, J=7.0 Hz), 6.44 (s, 1H), 7.04 (d, 2H, J=8.8 Hz), 7.31 (d, 2H, J=8.6 Hz), 7.67 (s, 1H), 7.86 (s, 1H); 19F NMR (d6-acetone/400 MHz) −79.5 (d, 3F, J=6.8 Hz); 13C NMR (d6-acetone/100 MHz) 13.8, 15.4, 61.3, 70.8 (q, J=32.8 Hz), 105.5, 115.2, 115.9, 117.5, 119.9, 123.8 (q, J=287.1 Hz), 129.8, 131.2, 135.5, 141.5, 153.1, 153.2, 157.4, 163.4; MS (ES+) 427 (M+1, 100); HRMS (ES+) m/z calcd for (C21H18O4ClF3) 427.0918, found 427.0921.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][CH2:15][CH2:16][CH3:17])[C:10](=[O:13])[CH2:11]Cl)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([SH:24])[C:19]1[O:23][CH:22]=[CH:21][CH:20]=1.[OH-].[Na+].C(=O)([O-])O.[Na+]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][CH2:15][CH2:16][CH3:17])[C:10](=[O:13])[CH2:11][S:24][CH2:18][C:19]1[O:23][CH:22]=[CH:21][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCC[C@H](NC(=O)OC(C)(C)C)C(=O)CCl
Reactant: SCc1ccco1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCCC[C@H](NC(=O)OC(C)(C)C)C(=O)CSCc1ccco1
Temperature: 25 °C
Reaction time: 17 h
Yield: 92.4 %

Procedure:
To a solution of (s)-3-tert-butoxycarbonylamino-1-chloro-2-heptanone (6.54 g) and furfurylmercaptan (3.11 g) in tetrahydrofuran (200 ml) was added 2N sodium hydroxide (13 ml), and the mixture was stirred at room temperature for 17 hours. Then, aqueous sodium hydrogencarbonate was added to the mixture, which was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and chromatographed on a silica gel column, eluting with hexane containing 10% ethyl acetate to give the titled product (7.82 g).
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][CH2:7][S:8]([O:11][CH2:12][C:13]([CH3:35])([CH3:34])[C@@H:14]([O:26]CC1C=CC=CC=1)[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2].C(O)(=O)C>[Pd].CO>[C:1]([NH:4][CH2:5][CH2:6][CH2:7][S:8]([O:11][CH2:12][C:13]([CH3:34])([CH3:35])[C@@H:14]([OH:26])[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:16])(=[O:9])=[O:10])(=[O:3])[CH3:2]
Reactant: CCOC(=O)OCCOC(=O)[C@H](OCc1ccccc1)C(C)(C)COS(=O)(=O)CCCNC(C)=O
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: CCOC(=O)OCCOC(=O)[C@H](O)C(C)(C)COS(=O)(=O)CCCNC(C)=O
Reaction time: 8 h
Yield: 84.2 %

Procedure:
Following the general procedure of hydrogenolysis of benzyl ethers of Description 18, a mixture of (ethoxycarbonyloxy)ethyl (2R)-4-{[3-(acetylamino)propyl]sulfonyloxy}-3,3-dimethyl-2-(phenylmethoxy)butanoate (32c) (5.2 g, 10 mmol), 1.3 g of 10 wt.-% of palladium on activated carbon in 20 mL of methanol (MeOH), and 1.0 mL (1.05 g, 17.5 mmol) of glacial acetic acid was stirred overnight under a hydrogen atmosphere. Upon the completion of reaction and following aqueous work-up, 3.6 g (84% yield) of the title compound (32) was obtained as a colorless, viscous oil. RT=21.95 min and 30.99 min (by LC/UV). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=0.99-1.01 (2s, 3H), 1.13-1.15 (2s, 3H), 1.32-1.37 (m, 3H), 1.59-1.62 (m, 3H), 2.00-2.01 (2s, 3H), 2.04-2.12 (m, 2H), 3.12-3.26 (m, 3H), 3.33-3.47 (m, 2H), 3.94-3.98 (m, 1H), 4.06-4.08 (2d, J=6.8, 6.0 Hz, 1H), 4.14-4.19 (2d, J=8.8, 8.8 Hz, 1H), 4.23-4.28 (m, 2H), 5.85-5.88 (br. m, 1H), 6.85 (m, 1H) ppm. MS (ESI) m/z: 428.14 (M+H)+, 450.14 (M+Na)+. The analytical data was consistent with the proposed structure.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([S:21]([NH2:24])(=[O:23])=[O:22])[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]([NH2:20])=[O:19])[CH:12]=2)[C:8]=1[O:9][CH3:10])=[O:2].[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][CH2:32][C:33](Cl)=[O:34])[CH:26]=1>>[CH:1]([C:3]1[CH:4]=[C:5]([S:21]([NH:24][C:33](=[O:34])[CH2:32][CH2:31][C:27]2[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=2)(=[O:23])=[O:22])[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]([NH2:20])=[O:19])[CH:12]=2)[C:8]=1[O:9][CH3:10])=[O:2]
Reactant: COc1c(C=O)cc(S(N)(=O)=O)cc1-c1cccc(NC(N)=O)c1
Reactant: O=C(Cl)CCc1cccnc1
Product: COc1c(C=O)cc(S(=O)(=O)NC(=O)CCc2cccnc2)cc1-c1cccc(NC(N)=O)c1

Procedure:
Proceeding as in Reference 21, but substituting 5-formyl-6-methoxy-3′-ureido-biphenyl-3-sulfonamide and 3-pyridin-3-ylpropanoyl chloride, gave 5-formyl-6-methoxy-N-(3-pyridin-3-ylpropanoyl)-3′-ureido-biphenyl-3-sulfonamide.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[CH3:20].[CH2:21]([Sn:25](Cl)([CH2:30][CH2:31][CH2:32][CH3:33])[CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][CH2:23][CH3:24].C(=O)(O)[O-].[Na+]>C1COCC1>[F:13][C:14]1[C:19]([Sn:25]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:30][CH2:31][CH2:32][CH3:33])[CH2:21][CH2:22][CH2:23][CH3:24])=[CH:18][N:17]=[CH:16][C:15]=1[CH3:20]
Reactant: Cc1cnccc1F
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cncc(C)c1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A THF (1 mL) solution of diisopropylamine (160 μL; WAKO) was cooled to −78° C. under a nitrogen atmosphere followed by the dropwise addition of normal butyllithium (2.6 M, 430 μL; KANTO). The resulting mixture was stirred as it was for 30 minutes followed by the dropwise addition of a THF (1 mL) solution of 4-fluoro-3-methylpyridine (111 mg) and the resulting mixture was further stirred for 1 hour. Then tri-n-butyltin chloride (330 μL; TCI) was added and the resulting mixture was slowly raised to room temperature and then stirred for 2 hours. Saturated aqueous sodium bicarbonate solution was added to the reaction mixture solution, to the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine. The organic layer was dried and the solvent was evaporated under reduced pressure to give the title compound.
Reaction SMILES: [H-].[Na+].[C:3]1(=[O:9])[NH:7][C:6](=[O:8])[CH2:5][CH2:4]1.Cl.[N:11]1[CH:16]=[CH:15][C:14]([CH2:17]Cl)=[CH:13][CH:12]=1.C1CCCCC1>CN(C=O)C>[N:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:7]2[C:6](=[O:8])[CH2:5][CH2:4][C:3]2=[O:9])=[CH:13][CH:12]=1
Reactant: O=C1CCC(=O)N1
Reactant: ClCc1ccncc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCCCC1
Solvent: CN(C)C=O
Product: O=C1CCC(=O)N1Cc1ccncc1
Reaction time: 48 h

Procedure:
A suspension of sodium hydride (17.6 g, 0.44 mol) in DMF (500 mL) was stirred with ice bath cooling as succinimide (29.73 g, 0.3 mol) was cautiously added. 4-Picolyl chloride hydrochloride (32.81 g, 0.2 mol) was then added cautiously with vigorous stirring. The mixture was stirred at room temperature for 1 day and then at 100° C. for 2 days. The mixture was then cooled and filtered. The filtrate was concentrated in vacuo to give a black oil. This dark crude product was stirred four times with boiling cyclohexane (150 mL), each time decanting the boiling cyclohexane from the dark residue. Upon cooling the cyclohexane extracts, the desired product crystallized as colorless needles (23.05 g, 60.9%) which were filtered and air dried.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[C:9]1([S:15]([O:18][C:19]2[CH:27]=[CH:26][C:22]3[S:23][CH:24]=[CH:25][C:21]=3[CH:20]=2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>ClCCl>[C:5]([C:25]1[C:21]2[CH:20]=[C:19]([O:18][S:15]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)(=[O:16])=[O:17])[CH:27]=[CH:26][C:22]=2[S:23][CH:24]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)Cl
Reactant: O=S(=O)(Oc1ccc2sccc2c1)c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1csc2ccc(OS(=O)(=O)c3ccccc3)cc12
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 84 %

Procedure:
Powdered aluminum chloride (1.34 g, 10 mmol) was suspended in dichloromethane (10 ml). To the suspension was added dropwise acetyl chloride (1.02 ml, 14.3 mmol) over 5 minutes with stirring and under ice-cooling. Subsequently, a solution of the compound (8) (2.075 g, 7.2 mmol) prepared above in dichloromethane (6 ml) was added dropwise over 15 minutes. After being stirred for 2 hours at the same temperature and then for 2.5 hours at room temperature, the solution was poured into ice-water and extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from ethyl acetate (3 ml) and hexane (3 ml) to provide 2.01 g of the title compound (9). Yield: 84.4% mp 129-130° C.
Reaction SMILES: [Na].[NH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C:3]1=[O:11].[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[C:17](Cl)=[O:18]>C(O)C>[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[C:17]([CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[NH:2][C:3]1=[O:11])=[O:18]
Reactant: O=C1Cc2ccccc2N1
Reactant: O=C(Cl)c1ccco1
Agent: [Na]
Solvent: CCO
Product: O=C1Nc2ccccc2C1C(=O)c1ccco1
Reaction time: 0.21 h
Yield: 36.5 %

Procedure:
To a stirred solution of 5.5 g (0.24 mole) of sodium in 150 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole at room temperature. The resulting slurry was cooled to ice-bath temperature, and then 15.7 g (0.12 mole) of 2-furoyl chloride was added, dropwise, during 10-15 minutes. The ice-bath was removed, and an additional 100 ml of ethanol was added and then the reaction mixture was heated under reflux for 7 hours. The reaction mixture was allowed to stand overnight and then the solid was filtered off. The solid was added to 400 ml of water and the resulting mixture was acidified using concentrated hydrochloric acid. The mixture was cooled with ice and the solid was collected by filtration. The solid residue was recrystallized from 150 ml of acetic acid, affording 8.3 g of yellow crystals, m.p. 209°-210° C. (dec.).
Reaction SMILES: [NH2:1][C:2]1[N:3]([C:20](=[O:22])[NH2:21])[N:4]=[CH:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:8]=1.[CH:23]([O-])([O-])OCC.CN(C)C=O>C(OCC)(=O)C>[CH2:13]([C:10]1[CH:9]=[CH:8][C:7]([C:6]2[CH:5]=[N:4][N:3]3[C:20]([OH:22])=[N:21][CH:23]=[N:1][C:2]=23)=[CH:12][CH:11]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NC(=O)n1ncc(-c2ccc(Cc3ccccc3)cc2)c1N
Reactant: CCOC([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Oc1ncnc2c(-c3ccc(Cc4ccccc4)cc3)cnn12
Reaction time: 0.75 h

Procedure:
A mixture of 3-amino-4-(4-benzylphenyl)-2-carbamoylpyrazole (1.00 g), ethyl orthoformate (0.61 ml) and N, N-dimethylformamide (0.86 ml) was stirred at 100° C. to 110° C. for 45 minutes. To the reaction mixture was added ethyl acetate (20 ml). After stirring at room temperature for 30 minutes, the precipitate was separated by filtration, washed with ethyl acetate, and dried to give the title compound (0.72 g).
Reaction SMILES: [Mn]([O-])(=O)(=O)=[O:2].[K+].[N:7]1[CH:12]=[CH:11][CH:10]=[C:9]2[CH2:13][C:14]3[CH:20]=[C:19]([CH:21]([OH:25])[CH:22]([CH3:24])[CH3:23])[CH:18]=[CH:17][C:15]=3[O:16][C:8]=12>CC(C)=O>[C:21]([C:19]1[CH:18]=[CH:17][C:15]2[O:16][C:8]3=[N:7][CH:12]=[CH:11][CH:10]=[C:9]3[C:13](=[O:2])[C:14]=2[CH:20]=1)(=[O:25])[CH:22]([CH3:23])[CH3:24]
Reactant: CC(C)C(O)c1ccc2c(c1)Cc1cccnc1O2
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)C(=O)c1ccc2oc3ncccc3c(=O)c2c1
Temperature: 20 °C
Reaction time: 3 h

Procedure:
11 g of potassium permanganate is added in small portions to a solution of 6 g of 1-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)-2-methyl-1 -propanol in 160 ml of acetone, and the mixture is stirred at 20°C for 3 hours. The reaction mixture is filtered, and the residue is washed thoroughly with chloroform. The filtrate and washings are concentrated, and the residue is purified by column chromatography on silica gel with chloroform as eluent, and further by recrystallization from acetone to give 7-isobutyryl-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine melting at 155°-156°C.
Reaction SMILES: [CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][S:8][CH2:9][CH2:10][NH2:11].CS[C:14]1[NH:15][CH2:16][CH2:17][C:18]=1[N+:19]([O-:21])=[O:20]>C(O)C>[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][S:8][CH2:9][CH2:10][NH:11][C:14]1[NH:15][CH2:16][CH2:17][C:18]=1[N+:19]([O-:21])=[O:20]
Reactant: CSC1=C([N+](=O)[O-])CCN1
Reactant: Cc1[nH]cnc1CSCCN
Solvent: CCO
Product: Cc1[nH]cnc1CSCCNC1=C([N+](=O)[O-])CCN1
Yield: 65.9 %

Procedure:
A solution of 2-(5-methyl-4-imidazolylmethylthio)ethylamine (1.3 g, 0.0076 mol) and 2-methylthio-3-nitro-4,5-dihydropyrrole (1.2 g, 0.0075 mol) in ethanol (50 ml) was refluxed for 11/2 hours. The mixture was cooled, and the solid was filtered off and recrystallised from methanol/water to give 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-3-nitro-4,5-dihydropyrrole (1.4 g, 66%) m.p. 207.5°-208°. Found: C, 46.65; H, 6.15; N, 24.6; S, 11.5; C11H17N5O2S requires: C, 46.6; H, 6.05; N, 24.7; S, 11.3%.
Reaction SMILES: FC(F)(F)C([N:5]([CH2:16][CH:17]=[CH2:18])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13](Cl)=[O:14])=[CH:8][CH:7]=1)=O.C(N(CC)CC)C.[C:28]([CH:33]([CH:35]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[OH:36])[OH:34])([O:30][CH2:31][CH3:32])=[O:29]>CCOCC>[CH2:16]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([O:36][CH:35]([CH:33]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[OH:34])[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:14])=[CH:8][CH:7]=1)[CH:17]=[CH2:18]
Reactant: C=CCN(C(=O)C(F)(F)F)c1ccc(CC(=O)Cl)cc1
Reactant: CCOC(=O)C(O)C(O)C(=O)OCC
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C=CCNc1ccc(CC(=O)OC(C(=O)OCC)C(O)C(=O)OCC)cc1

Procedure:
A mixture of 4-[N-trifluoroacetyl-(allylamino)]phenylacetyl chloride and 1.2 g. triethylamine in 100 ml. warm ether is treated with 2.5 g. diethyl tartrate and refluxed for 24 hours. The hot solution is filtered, the residue is washed with hot ether, and the solution is evaporated. After treatment with aqueous methanolic potassium carbonate, the product is precipitated by acidification, filtered, and dried. Crystallization from acetone yields diethyl O-[4-(allylamino)phenylacetyl]tartrate as a white, crystalline solid.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[CH3:7][N:8]([CH3:13])[S:9](Cl)(=[O:11])=[O:10].C(N(CC)CC)C>ClCCl>[CH3:7][N:8]([CH3:13])[S:9]([N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH3:1])(=[O:11])=[O:10]
Reactant: Cc1ncc[nH]1
Reactant: CN(C)S(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1nccn1S(=O)(=O)N(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.8 %

Procedure:
To a solution of 2-methyl-1H-imidazole (10 g, 121.8 mmol) in dichloromethane (100 mL) was added N,N-dimethylsulfamoyl chloride (14.4 mL, 133.7 mmol) and triethylamine (34 mL, 244.1 mmol). The reaction mixture was stirred overnight at room temperature, then quenched with 10 mL of water and extracted with 1×50 mL of DCM. The organic layer was washed with 2×20 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:2) as the eluent to furnish 20 g (87%) of the title compound as a yellow oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[CH:3][CH:2]=1.Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1)=[O:10]>>[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:9](=[O:10])[O:11][C:12]2[CH:13]=[CH:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][CH:17]=2)=[CH:3][CH:2]=1
Reactant: Nc1ccncc1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Product: O=C(Nc1ccncc1)Oc1ccc([N+](=O)[O-])cc1

Procedure:
Prepared as Example 27d from pyridin-4-amine and p-nitrophenyl chloroformate to provide the compound as an off white solid. MS=260 (MH+).