Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.Br[CH2:9][C:10]1[S:14][C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:12][CH:11]=1>CN(C=O)C>[N:3]1([CH2:9][C:10]2[S:14][C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:12][CH:11]=2)[CH:7]=[CH:6][N:5]=[CH:4]1
Reactant: c1c[nH]cn1
Reactant: CCOC(=O)c1ncc(CBr)s1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1ncc(Cn2ccnc2)s1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 44 %

Procedure:
To a cooled (0 C) suspension of sodium hydride (60% in oil, 82 mg, 2.05 mmol) in dry DMF (2 ml) was added imidazole (93 mg, 1.37 mmol) as a solution in dry DMF (0.5 ml). Mixture was stirred at RT 45 min, cooled to 0° C. followed by addition of ethyl 5-(bromomethyl)thiazole-2-carboxylate (342 mg, 1.37 mmol) dissolved in dry DMF (2 ml). After being stirred at RT for 20 h, the reaction mixture was evaporated and the residue was taken up in DCM and washed twice with saturated NaCl solution. Thus, 143 mg (44%) of the title compound was obtained. 1H-NMR (400 MHz; d6-DMSO): δ 1.32 (t, 3H), 4.37 (q, 2H), 5.39 (s, 2H), 6.91 (s, 1H), 7.20 (s, 1H), 7.75 (s, 1H), 7.93 (s, 1H).
Reaction SMILES: C(O[C:4](=[O:27])[CH2:5][N:6]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:7][CH2:8][CH2:9][C:10]1[CH:19]=[CH:18][C:17]2[CH2:16][CH2:15][CH2:14][NH:13][C:12]=2[N:11]=1)C.[OH-].[Na+].Cl.C(N(CC)CC)C.Cl.[CH3:39][NH:40][O:41][CH3:42].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(O)C.O>[C:23]([O:22][C:20](=[O:21])[N:6]([CH2:5][C:4](=[O:27])[N:40]([O:41][CH3:42])[CH3:39])[CH2:7][CH2:8][CH2:9][C:10]1[CH:19]=[CH:18][C:17]2[CH2:16][CH2:15][CH2:14][NH:13][C:12]=2[N:11]=1)([CH3:24])([CH3:25])[CH3:26]
Reactant: CNOC
Reactant: CCOC(=O)CN(CCCc1ccc2c(n1)NCCC2)C(=O)OC(C)(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: CON(C)C(=O)CN(CCCc1ccc2c(n1)NCCC2)C(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 1 h

Procedure:
To a solution of 2-8 (1.49 g, 3.96 mmol) in ethanol (8 mL) was added NaOH (4.36 mL 1M solution in water, 4.36 mmol). After stirring for 1 h at 50° C., HCl (4.75 mL of a 1M solution in water, 4.75 mmol) was added, and the mixture evaporated to give an oily residue. The residue was evaporated from ethanol three times, and then from acetonitrile three times, producing a yellow crusty solid which was dried under a vacuum of <2 mm Hg for 2 h. This residue was then slurried in chloroform (15 mL), and triethylamine (2.75 mL, 19.8 mmol), N,O-dimethylhydroxylamine hydrochloride (0.772 g, 7.92 mmol), HOBT (1 g) and EDC (0.91 g, 4.75 mmol) were added. After stirring for 15 h, the mixture was evaporated to dryness, the residue slurried in EtOAc, washed with sat. NaHCO3, brine, and dried over Na2SO4. Evaporative removal of the solvent gave 2-9 as a yellow oil. TLC Rf =0.49 (silica, 70:25:5 chloroform /ethyl acetate /methanol) 1H NMR (300 MHz, CDCl3) δ 7.05 (m, 1H), 6.38 (m, 1H), 4.81 (br s, 1H), 3.69, m, 3H), 3.37 (m, 4H), 3.18 (s, 3H), 2.64 (m, 2H), 2.53 (m, 2H), 1.88 (m, 4H), 1.44 (m, 9H).
Reaction SMILES: [CH3:1][C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH3:11].[CH3:12][O:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[C:16](=[O:19])[CH2:17]Br.Br>>[CH3:1][C:2]1[N:10]=[C:5]2[N:6]([CH2:17][C:16]([C:15]3[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=3[O:13][CH3:12])=[O:19])[CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH3:11]
Reactant: COc1ccccc1C(=O)CBr
Reactant: Cc1[nH]c2ncccc2c1C
Agent: Br
Product: COc1ccccc1C(=O)Cn1cccc2c(C)c(C)nc1-2

Procedure:
The title compound was prepared on a 1 mmol scale from 2,3-dimethylpyrrolo[2,3-b]pyridine and o-methoxyphenacyl bromide in the same manner as described in example 27 yielding 244 mg (71%) pure hydrobromide as a light yellow solid.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][C:8]([C:11]3[CH:21]=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][CH:12]=3)=[CH:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[H][H]>CCOC(C)=O.[Pt](=O)=O>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:12]=[CH:13][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:20][CH:21]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: CCOC(=O)c1ccc(C2=CCC3(CC2)OCCO3)cc1
Agent: O=[Pt]=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(C2CCC3(CC2)OCCO3)cc1
Reaction time: 1 h

Procedure:
A solution of the title compound from Example 10 Step A (907 mg, 3.15 mmol) in EtOAc was degassed via nitrogen sparge. Platinum(IV) oxide (225 mgs, 0.991 mmol) was then added. The reaction flask was fitted with a 3-way adapter equipped with a hydrogen balloon. After 3 vacuum/hydrogen cycles, the reaction mixture was placed under a hydrogen atmosphere. After 1 h, the reaction mixture was filtered through a pad of Celite, rinsing with EtOAc, and concentrated in vacuo. The unpurified product was used in the subsequent step: LCMS m/z 291.0 [M+H]+.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11](=[O:27])[C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][N:21]4[CH3:26])=[CH:14][CH:13]=3)=[C:9]([C:28]3[CH:33]=[CH:32][C:31]([O:34]C)=[CH:30][CH:29]=3)[S:8][C:7]=2[CH:36]=1.C(S)C.[Cl-].[Al+3].[Cl-].[Cl-]>>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11](=[O:27])[C:12]3[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][N:21]4[CH3:26])=[CH:16][CH:17]=3)=[C:9]([C:28]3[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=3)[S:8][C:7]=2[CH:36]=1
Reactant: COc1ccc(-c2sc3cc(OC)ccc3c2C(=O)c2ccc(OCC3CCCCN3C)cc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCS
Product: CN1CCCCC1COc1ccc(C(=O)c2c(-c3ccc(O)cc3)sc3cc(O)ccc23)cc1
Yield: 60.9 %

Procedure:
6-Methoxy-2-(4-methoxyphenyl)-3-(4-[(1-methylpiperidin-2-yl)methoxy]benzoyl)benzo[b]thiophene (339 mg, 0.676 mmol), ethane thiol (8.75 mmol), and aluminum chloride (541 mg, 4.06 mmol) were converted to 195 mg (61%) of the title compound by the procedure of Example 16. MS(FD) 473(M+). IR (CHCl3) ν max 3414, 3179, 1605, 1468, 1261, 1170.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:7]([OH:9])=O)=[N:4][O:5][N:6]=1.[Cl:10][C:11]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:12]=1[NH2:13]>>[NH2:1][C:2]1[C:3]([C:7]([NH:13][C:12]2[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:11]=2[Cl:10])=[O:9])=[N:4][O:5][N:6]=1
Reactant: Nc1cc(Cl)ccc1Cl
Reactant: Nc1nonc1C(=O)O
Product: Nc1nonc1C(=O)Nc1cc(Cl)ccc1Cl

Procedure:
This compound was prepared according to the procedure of Example 45, Step 1, using 4-amino-1,2,5-oxadiazole-3-carboxylic acid and 2,5-dichloroaniline as the starting materials. LCMS for C9H7Cl2N4O2 (M+H)+: m/z=273.0.
Reaction SMILES: [BH4-].[Li+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:27](OC)=[O:28])=[C:8]2[C:12]=1[N:11]=[C:10]1[N:13]([C:17]3[C:18]([CH3:26])=[N:19][C:20]([O:24][CH3:25])=[N:21][C:22]=3[CH3:23])[CH2:14][CH2:15][CH2:16][N:9]21>O1CCCC1>[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[C:18]([CH3:26])=[N:19][C:20]([O:24][CH3:25])=[N:21][C:22]=4[CH3:23])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH2:27][OH:28])=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(Cl)c2nc3n(c12)CCCN3c1c(C)nc(OC)nc1C
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1nc(C)c(N2CCCn3c2nc2c(Cl)ccc(CO)c23)c(C)n1
Temperature: 40 °C
Reaction time: 14 h
Yield: 97.7 %

Procedure:
Lithium borohydride (1.93 g, 88.4 mmol) was added to a stirred solution of methyl 9-chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (8.87 g, 22.1 mmol) in tetrahydrofuran (100 mL) at room temperature, and the mixture was stirred at 40° C. for 14 hr. The reaction was quenched by methanol, and the mixture was diluted with aqueous saturated ammonium chloride at 0° C. The mixture was extracted with tetrahydrofuran/ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was washed with ethyl acetate/diisopropyl ether to give the title compound as a colorless powder (8.08 g, 21.6 mmol, 98%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[CH:5]=[C:6]([CH3:9])[C:7]=1[OH:8].[C:20](Cl)(=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>[Na].C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[CH:5]=[C:6]([CH3:9])[C:7]=1[O:8][C:20](=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCCCC(=O)Cl
Reactant: Cc1cc(C2CC(C)(C)NC(C)(C)C2)cc(C)c1O
Agent: [Na]
Solvent: Cc1ccccc1C
Product: CCCCCCCC(=O)Oc1c(C)cc(C2CC(C)(C)NC(C)(C)C2)cc1C

Procedure:
20 Parts of 4-(3',5'-dimethyl-4'-hydroxyphenyl)-2,2,6,6-tetramethylpiperidine were dissolved in 1000 parts of sodium dried xylene and heated to reflux whilst stirred. 6.3 Parts of octanoyl chloride dissolved in a small amount of xylene were added to the refluxing solution dropwise. The solution was heated at reflux overnight, allowed to cool and filtered. The filtrate was evaporated to low bulk, dissolved in ether and washed with 2% aqueous sodium hydroxide and water. The organic phase was dried over magnesium sulphate and evaporated under reduced pressure. The residue was distilled under reduced pressure to yield 10.3 parts of the desired product having boiling point 175°-178°/0.05 mm and the following elemental analysis
Reaction SMILES: C([O:4][CH2:5][C:6]([N:8]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[O:29][CH3:30])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7])(=O)C.C(=O)([O-])[O-].[K+].[K+].O>CO>[OH:4][CH2:5][C:6]([N:8]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[O:29][CH3:30])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7]
Reactant: COc1ccccc1CN(C(=O)COC(C)=O)c1ccccc1Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1ccccc1CN(C(=O)CO)c1ccccc1Oc1ccccc1
Temperature: 50 °C
Reaction time: 7 h
Yield: 95.6 %

Procedure:
In 6 ml of methanol was dissolved 525 mg of N-acetoxyacetyl-N-(2-methoxybenzyl)-2-phenoxyaniline, and then 537 mg of potassium carbonate was added, followed by stirring at 50° C. for 7 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with 5% hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate-hexane=1:3) and allowed to stand at room temperature to give 450 mg of N-hydroxyacetyl-N-(2-methoxybenzyl)-2-phenoxyaniline as crystals.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1I.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].CCOCC>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:23]1[S:22][CH:26]=[CH:25][CH:24]=1
Reactant: OB(O)c1cccs1
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: COCCOC
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1cccs1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.45 g) in dimethoxyethane (4 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.035 g) was stirred at room temperature for 30 minutes and then heated to 80° C. Thiophene-2-boronic acid (0.14 g) and aqueous sodium carbonate solution (2 ml, 1M) were added and the mixture heated under reflux for 3 hours. The cooled reaction was poured into ether and water. The organic layer was separated, dried (MgSO4) and evaporated. The residue was taken up the minimum amount of dichloromethane and silica gel (10 g) added. The solvent was removed and the residue applied to a column of silica gel (75 g) which was eluted with hexane containing increasing proportions of dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a white solid. A sample recrystallised form methanol had m.p. 206-7° C.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[CH3:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.S(Cl)(Cl)=O>C(Cl)(Cl)Cl>[CH3:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[S:2]([Cl:1])(=[O:5])=[O:3]
Reactant: O=S(=O)(O)Cl
Reactant: Cc1cnc2ccccc2c1
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: Cc1cnc2c(S(=O)(=O)Cl)cccc2c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 34.3 %

Procedure:
To 9.0 mL (135 mmol, Fisher) of chlorosulfonic acid was added dropwise with stirring at room temperature 5.00 g (35.0 mmol, Lancaster) of 3-methyl-quinoline over ~5 minutes. The addition was exothermic. The resulting dark solution was heated to 140°-145°, stirring for 5 h, then cooled to 125°. To the cooled reaction mixture was added dropwise over 15 rain 3.3 mL (45 mmol, Mallinckrodt) of thionyl chloride, and the reaction mixture was then heated to 1400 for 1 h. The reaction mixture was cooled to room temperature, then cooled in an ice-bath and added slowly to 50 g of ice. Chloroform (50 mL) was added to the resulting slurry and stirred until the ice melted to give two layers. The aqueous layer was separated and extracted with 30 mL of chloroform. The chloroform layers were combined, washed with two-50 mL portions of 5% aqueous sodium bicarbonate solution, 50 mL of water, dried (sodium sulfate) and concentrated in vacuo to give 4.6 g of a crude light brown solid. The crude material was recrystallized (~20 mL toluene), and the crystals were washed with hexane and dried in vacuo to afford 2.89 g (12.0 mmol, 34%) of title compound as small pale brown crystals, mp 158°-159°.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11](/[CH:15]=[CH:16]/[CH:17]=[CH:18]/[C:19]([O:21]CC)=[O:20])=[CH:10][C:9]=1[CH3:24].[OH-].[Na+]>CO.O>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:9]([CH3:24])=[CH:10][C:11](/[CH:15]=[CH:16]/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20])=[CH:12][C:13]=1[CH3:14]
Reactant: CCOC(=O)/C=C/C=C/c1cc(C)c(OCOCCOC)c(C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COCCOCOc1c(C)cc(/C=C/C=C/C(=O)O)cc1C
Yield: 85.4 %

Procedure:
To a stirred solution of ethyl 5-[4-{(2-methoxyethoxy)methoxy}-3,5-dimethylphenyl]-(2E,4E)-2,4-pentadienoate (5.28 g) in methanol (55 ml) was added a solution of sodium hydroxide (6.32 g) in water (18 ml) below 20° C. After being stirred for an hour, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in water (200 ml) and adjusted to pH 4 with 10% hydrochloride solution. The resulting precipitate was collected by filtration and washed with water to give yellowish powder of 5-[4-{(2-methoxyethoxy)methoxy}-3,5-dimethylphenyl]-(2E,4E)-2,4-pentadienoic acid (4.13 g).
Reaction SMILES: N[C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([Cl:17])[CH:11]=2)=[CH:4][N:3]=1.C(=O)(O)O.[NH2:22][C:23]([NH2:25])=[NH:24]>CN(C)C(=O)C>[NH2:24][C:23]1[N:25]=[C:8]([NH2:9])[C:7]2[C:2](=[N:3][CH:4]=[C:5]([C:10]3[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([Cl:17])[CH:11]=3)[N:6]=2)[N:22]=1
Reactant: N#Cc1nc(-c2cc(Cl)cc(Cl)c2)cnc1N
Reactant: N=C(N)N
Agent: O=C(O)O
Solvent: CC(=O)N(C)C
Product: Nc1nc(N)c2nc(-c3cc(Cl)cc(Cl)c3)cnc2n1

Procedure:
This compound is prepared in a manner analogous to that of Step B of Example 4, using 0.8 gram (0.003 mole) of 2-amino-3-cyano-5-(3,5-dichlorophenyl)pyrazine and 1.3 grams (0.007 mole) of guanidine carbonate in 10 mL of N,N-dimethylacetamide, yielding 2,4-diamino-6-(3,5-dichlorophenyl)pteridine.
Reaction SMILES: Br[C:2]([CH3:7])([CH3:6])[C:3](Br)=[O:4].[Al+3].[Cl-].[Cl-].[Cl-].[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][CH2:13]1>C(Cl)Cl>[CH3:6][CH:2]1[C:3](=[O:4])[C:18]2=[CH:17][C:16]3[CH2:15][CH2:14][CH2:13][CH2:12][C:21]=3[CH:20]=[C:19]2[CH2:7]1
Reactant: CC(C)(Br)C(=O)Br
Reactant: c1ccc2c(c1)CCCC2
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC1Cc2cc3c(cc2C1=O)CCCC3
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 31.1 %

Procedure:
A total of 145 g (0.63 mol) of 2-bromo-2-methylpropanoyl bromide were added dropwise to a suspension of 223 g (1.67 mol) AlCl3 in 200 ml of CH2Cl2 with vigorous stirring for 15 min at 0° C. This mixture was stirred for 45 min at this temperature; then a solution of 83.4 g (0.63 mol) of tetraline in 200 ml of CH2Cl2 was added dropwise. The mixture was slowly warmed to ambient temperature, stirred additionally overnight, and, then, poured on 1000 cm3 of ice. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of CH2Cl2. The combined organic fractions were dried over MgSO4 and evaporated to dryness. Fractional distillation gave a yellowish mixture of the title indanones, b.p. 183-190° C./7 mm Hg. This mixture was recrystallized from 300 ml of n-hexane. Crystals of 2-methyl-1,2,6,7,8,9-hexahydro-3H-cyclopenta[a]naphthalen-3-one that precipitated at −30° C. were filtered off, washed with 2×25 ml of cold n-hexane, and dried in vacuum. Yield 56.5 g (45%). The filtrate was evaporated to dryness and dried in vacuum. This procedure gave 39.3 g (31%) of pure 2-methyl-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]naphthalen-1-one.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[C:6]([CH:9]=1)[C:7]#[N:8].B.C1C[O:22][CH2:21]C1.N1(C(N2C=CN=C2)=O)C=CN=C1.CC([O-])(C)C.[K+]>C1COCC1>[Br:1][C:2]1[CH:9]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[Cl:17])[C:21](=[O:22])[NH:8][CH2:7]2
Reactant: N#Cc1cc(Br)ccc1Nc1ccccc1Cl
Reactant: C1CCOC1
Agent: B
Agent: CC(C)(C)[O-]
Agent: O=C(n1ccnc1)n1ccnc1
Product: O=C1NCc2cc(Br)ccc2N1c1ccccc1Cl

Procedure:
To a stirred solution of 5-bromo-2-(2-chlorophenylamino)benzonitrile (0.8201 g, 2.67 mmol) in THF (10.00 ml, 2.67 mmol) was slowly added borane-THF (10.7 ml, 10.7 mmol) at RT for 10 min and the resulting mixture was stirred continuously over night. The mixture was quenched with slow addition of MeOH until all bubbling subsided. The mixture was concentrated in vacco. The residue was diluted with NaHCO3(aq) and water (5 mL each) and the separated aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to give the crude residue, which was taken up in THF (8.00 ml) and treated with di(1H-imidazol-1-yl)methanone (0.519 g, 3.20 mmol) at RT. After stirring for 30 min, to the mixture was added potassium 2-methylpropan-2-olate (0.748 g, 6.67 mmol). The suspension was stirred at RT for 1 h and washed with EtOAc-ether to give 6-bromo-1-(2-chlorophenyl)-3,4-dihydroquinazolin-2(1H)-one as a white solid. MS m/e 336 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][N:14]=1)[CH2:5][C:6](=O)[CH2:7][C:8](=O)C.Cl.[CH3:16][C:17]1[CH:18]=[C:19]([NH:23][NH2:24])[CH:20]=[CH:21][CH:22]=1.[OH-].N>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([CH3:16])[CH:18]=3)[N:24]=[C:7]([CH3:8])[CH:6]=2)[CH:12]=[CH:13][N:14]=1
Reactant: Cc1cccc(NN)c1
Reactant: CC(=O)CC(=O)Cc1ccnc(Cl)c1
Agent: Cl
Agent: N
Agent: [OH-]
Solvent: CCO
Product: Cc1cccc(-n2nc(C)cc2-c2ccnc(Cl)c2)c1
Yield: 72.2 %

Procedure:
To a mixture of 1-(2-chloroisonicotinyl)-1,3-butanedione (1.35 g, 0.068 mol) and 3-methylphenylhydrazine hydrochloride (1.30 g, 0.0082 mol) in ethanol (40 mL) was added ammonia hydroxide (0.96 mL, 0.0082 mol) dropwise. The reaction mixture was heated at reflux overnight. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and the crude was purified by chromatography on silica gel (ethyl acetate/hexane, 2:8) to give 1.68 g (87% yield) of product as a yellow oil: Anal. Calcd. for C16H14ClN3: C, 67.72; H, 4.97; N, 14.81; Cl, 12.49. Found: C, 67.91; H, 5.08; N, 14.79; Cl, 12.40.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][S:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)(=[O:9])=[O:8].[CH3:22]I.O>CN(C)C=O>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH3:22])[S:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)(=[O:9])=[O:8]
Reactant: CI
Reactant: O=S(=O)(NCCCCO)c1ccc(-c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Product: CN(CCCCO)S(=O)(=O)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 80 %

Procedure:
The title compound was prepared from biphenyl-4-sulfonic acid-(4-hydroxybutyl)-amide (0.4 g), methyl iodide (0.2 mL) and K2CO2 (0.5 g) in dimethylformamide (20 mL). The mixture was stirred at room temperature for 4 hours, poured into water and extracted with diethyl ether. The organic phase was repeatedly washed with water and evaporated to give the title compound as a white solid (80%). δC (DMSO, 62.9 MHz): 23.7, 29.5, 34.5, 49.6, 60.2, 127.1, 127.2, 127.6, 128.6, 129.2, 135.8, 138.4 and 144.3. δH (DMSO, 250 MHz): 1.45 (4H, m), 2.68 (3H, s), 2.97 (2H, t, J 7.0), 3.40 (2H, m), 7.49 (3H, m), 7.75 (2H, d, J 7.0), 7.83 (2H, d, J 8.5) and 7.91 (2H, d, J 8.2).
Reaction SMILES: [CH:1]([NH:5][C:6]1[S:7][C:8]2[C:13]([N:14]=1)=[CH:12][CH:11]=[C:10]([CH:15]=[O:16])[N:9]=2)([CH2:3][CH3:4])[CH3:2].[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]([N+:35]#[C-:36])S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CCO>[CH:1]([NH:5][C:6]1[S:7][C:8]2[C:13]([N:14]=1)=[CH:12][CH:11]=[C:10]([C:15]1[O:16][CH:36]=[N:35][C:24]=1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[F:17])[N:9]=2)([CH2:3][CH3:4])[CH3:2]
Reactant: [C-]#[N+]C(c1ccccc1F)S(=O)(=O)c1ccc(C)cc1
Reactant: CCC(C)Nc1nc2ccc(C=O)nc2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCC(C)Nc1nc2ccc(-c3ocnc3-c3ccccc3F)nc2s1
Temperature: 25 °C
Yield: 29.9 %

Procedure:
A solution of 2-(sec-butylamino)thiazolo[5,4-b]pyridine-5-carbaldehyde (presumed 0.24 mmol, 1.0 eq.), 1-fluoro-2-(isocyano(tosyl)methyl)benzene (0.0874 g, 0.302 mmol, 1.3 eq.), and K2CO3 (0.0654 g, 0.473 mmol, 2.0 eq.) in EtOH (2.4 mL) was refluxed overnight. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and the residue was taken up in EtOAc and water. After separation of the layers, the organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give N-sec-butyl-5-(4-(2-fluorophenyl)oxazol-5-yl)thiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.0264 g, 30% yield). LC/MS (MH)=369.20.