Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH2:11])[CH:3]=1.B(O)(O)[C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1>>[C:16]1([CH3:19])[CH:17]=[CH:18][C:13]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH2:11])[CH:3]=2)=[CH:14][CH:15]=1
Reactant: Nc1cc(Cl)n2nccc2n1
Reactant: Cc1ccc(B(O)O)cc1
Product: Cc1ccc(-c2cc(N)nc3ccnn23)cc1

Procedure:
The titled compound was prepared using a procedure analogous to that described in connection with Example 15 except that 7-chloropyrazolo[1,5-a]pyrimidin-5-amine (1E) and p-tolylboronic acid were used as starting materials. 1H NMR (400 MHz, CHLOROFORM-d) δ 2.44 (s, 3H), 4.82 (s, 2H), 6.16 (s, 1H), 6.20 (d, J=2.0 Hz, 1H), 7.34 (d, J=8.1 Hz, 2H), 7.81 (d, J=8.1 Hz, 2H), 7.91 (d, J=2.0 Hz, 1H).
Reaction SMILES: [CH:1]1([C:4]2[S:8][C:7]([N:9]=[C:10]=[O:11])=[N:6][N:5]=2)[CH2:3][CH2:2]1.[CH2:12]([NH:15][CH2:16][CH2:17][CH:18]=[O:19])[C:13]#[CH:14]>C1C=CC=CC=1>[CH2:12]([N:15]([CH2:16][CH2:17][CH:18]=[O:19])[C:10]([NH:9][C:7]1[S:8][C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:5][N:6]=1)=[O:11])[C:13]#[CH:14]
Reactant: C#CCNCCC=O
Reactant: O=C=Nc1nnc(C2CC2)s1
Solvent: c1ccccc1
Product: C#CCN(CCC=O)C(=O)Nc1nnc(C2CC2)s1

Procedure:
A mixture of 5-cyclopropyl-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05 mole), the dimethyl acetal of 3-propargylaminopropionaldehyde (0.1 mole) and benzene (60 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and reflux condenser. The reaction mixture is heated at reflux for a period of about 15 minutes. After this time the mixture is stripped of benzene under reduced pressure to yield a solid product as the residue. The residue is then recrystallized to yield the desired product the dimethyl acetal of 3-[1-propargyl-3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]1([CH2:17][CH3:18])[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[NH:8][C:7]1=[O:16].[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1>>[CH2:17]([C:6]1([CH2:5][CH2:4][CH2:3][CH2:2][N:29]2[CH2:28][CH2:27][N:26]([C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][CH:24]=3)[CH2:31][CH2:30]2)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[NH:8][C:7]1=[O:16])[CH3:18]
Reactant: Fc1ccc(N2CCNCC2)cc1
Reactant: CCC1(CCCCCl)C(=O)Nc2ccc(F)cc21
Product: CCC1(CCCCN2CCN(c3ccc(F)cc3)CC2)C(=O)Nc2ccc(F)cc21

Procedure:
The title compound is prepared according to process H by applying processing method 1 starting from 3-(4-chlorobutyl)-3-ethyl-5-fluoro-1,3-dihydro-2H-indol-2-one and 1-(4-fluorophenyl)-piperazine.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])=[C:4]([F:17])[CH:3]=1.O1C=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C(Cl)Cl.[F-].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CS(C)=O>[C:20]([CH2:21][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])=[C:4]([F:17])[CH:3]=1)#[N:19]
Reactant: C[C@H](N[S@](=O)C(C)(C)C)c1ccc(Br)cc1F
Reactant: CC1(C)OB(c2cnoc2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [F-]
Solvent: ClCCl
Solvent: CS(C)=O
Product: C[C@H](N[S@](=O)C(C)(C)C)c1ccc(CC#N)cc1F
Temperature: 130 °C
Yield: 51.6 %

Procedure:
To a microwave vial with a stir bar was added (R)—N—((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (300 mg, 0.93 mmol), 4-isoxazoleboronic acid pinacol ester (218 mg, 1.12 mmol), PdCl2(dppf).CH2Cl2 adduct (76 mg, 0.09 mmol), potassium fluoride (2.7 mL, 1.0 M in water, 2.79 mmol) and finally DMSO (9 mL). The reaction mixture was degassed with bubbling nitrogen (3 min) and the vial capped and heated in a preheated oil bath at 130° C. for 18 hours. The reaction mixture was diluted with a saturated solution of NH4Cl and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptanes 40 to 100%) provided (R)—N—((S)-1-(4-(cyanomethyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (136 mg, 0.48 mmol, 52% yield) as a viscous brown oil. 1H NMR (400 MHz, CDCL3) δ 1.19 (s, 9H) 1.57 (d, J=6.80 Hz, 3H) 3.39 (d, J=4.35 Hz, 1H) 3.74 (s, 2H) 4.81-4.88 (m, 1H) 7.04 (d, J=10.66 Hz, 1H) 7.11 (d, J=7.97 Hz, 1H) 7.38 (t, J=7.73 Hz, 1H). LCMS m/z 283.0 (M+H)+, Rt 0.72 min.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]1[N:15]=[N:16][C:17]([S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])=[C:8]1[NH:7][C:6]2=O.O=P(Cl)(Cl)[Cl:30]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:30][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]2[N:15]=[N:16][C:17]([S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])=[C:8]2[N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1cc2c(=O)[nH]c3c(S(=O)(=O)c4ccccc4)nnn3c2cc1OC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Product: COc1cc2c(Cl)nc3c(S(=O)(=O)c4ccccc4)nnn3c2cc1OC
Temperature: 120 °C
Yield: 59 %

Procedure:
A mixture of 7,8-dimethoxy-3-(phenylsulfonyl)-[1,2,3]triazolo[1,5-a]quinazolin-5(4H)-one (262 mg, 0.68 mmol) and tetrabutylammonium chloride (189 mg, 0.68 mmol) in POCl3 (10 mL) was heated at 120° C. for 30 min and then cooled to room temperature. After removal of POCl3 in vacuo, the residue was purified by column chromatography on silica gel eluting with 30% ethyl acetate in hexane to yield 5-chloro-7,8-dimethoxy-3-(phenylsulfonyl)-[1,2,3]triazolo[1,5-a]quinazoline (162 mg, 59%). 1H NMR (CDCl3, 600 MHz) δ 8.28-8.26 (m, 2H), 8.04 (s, 1H), 7.61 (s, 1H), 7.60-7.58 (m, 1H); 7.56-7.54 (m, 2H), 4.18 (s, 3H), 4.10 (s, 3H); MS (ES+) m/z 405.0 (M+H)+
Reaction SMILES: [Cl-].N[C:3]1[C:4]([CH3:25])=[CH:5][C:6]2[C:15]([CH:16]=1)=[N+:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:13]1[C:8](=[CH:9][C:10]([CH3:24])=[C:11]([NH2:23])[CH:12]=1)[N:7]=2.[F:26][B-:27]([F:30])([F:29])[F:28].[H+].[S-:32][C:33]#[N:34].[Na+].N([O-])=O.[Na+]>>[F:26][B-:27]([F:30])([F:29])[F:28].[NH2:23][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[CH3:24])[N:7]=[C:6]1[C:15]([CH:16]=[C:3]([S:32][C:33]#[N:34])[C:4]([CH3:25])=[CH:5]1)=[N+:14]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Cc1cc2nc3cc(C)c(N)cc3[n+](-c3ccccc3)c2cc1N
Reactant: N#C[S-]
Agent: F[B-](F)(F)F
Agent: O=N[O-]
Agent: [Cl-]
Product: Cc1cc2nc3cc(C)c(SC#N)cc3[n+](-c3ccccc3)c2cc1N
Temperature: 50 °C

Procedure:
1 g of 3,7-diamino-2,8-dimethyl-5-phenyl-phenazinium chloride were suspended in 15 ml of 50 wt.-% tetrafluoroboric acid and heated to 50° C. Then, 10 ml of an aqueous solution consisting of 1.109 g sodium thiocyanate and 454 mg of sodium nitrite were added dropwise over one hour at a temperature of 50 to 60° C. and thereafter stirred for another hour at this temperature. The reaction formulation was cooled down to room temperature, the resulting black solid matter was filtered away and dried. The yield was 812 mg (64.0% of the theory).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)=[C:9]([C:27]2[N:31]([CH3:32])[N:30]=[N:29][N:28]=2)[CH:10]=[CH:11][CH:12]2OC3(CCCCC3)[O:15][CH:14]([CH2:23][C:24]([OH:26])=[O:25])[CH2:13]2)=[CH:4][CH:3]=1>C1COCC1>[F:39][C:36]1[CH:37]=[CH:38][C:33]([C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[C:9]([C:27]2[N:31]([CH3:32])[N:30]=[N:29][N:28]=2)[CH:10]=[CH:11][C@@H:12]2[O:26][C:24](=[O:25])[CH2:23][C@@H:14]([OH:15])[CH2:13]2)=[CH:34][CH:35]=1
Reactant: Cn1nnnc1C(C=CC1CC(CC(=O)O)OC2(CCCCC2)O1)=C(c1ccc(F)cc1)c1ccc(F)cc1
Solvent: C1CCOC1
Product: Cn1nnnc1C(C=C[C@H]1C[C@H](O)CC(=O)O1)=C(c1ccc(F)cc1)c1ccc(F)cc1
Reaction time: 26 h
Yield: 16.7 %

Procedure:
A mixture of 4-[4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-1,5-dioxaspiro[5.5]undecane-2-acetic acid (280 mg, 0.52 mmol) in 20 mL of THF/0.5N HCl (1:1) was allowed to stand at ambient temperature for 26 hours. The solution was partitioned between brine and ethyl acetate. The organic layer was washed with brine (2x), dried (Na2SO4) and concentrated. The resultant foam (126 mg) was dissolved in dry methylene chloride (10 mL) and treated with 1-cyclohexyl-3-(2-morpholinomethyl) carbodiimide metho-p-toluenesulfonate (0.24 g). After 16 hours at ambient temperature, the solution was evaporated under reduced pressure and the residue was purified by silica gel chromatography using ethyl acetate as eluent. The appropriate fractions afforded 38 mg (16.6%) of the title compound as a colorless oil which is a racemic mixture of the compound of Example 7.
Reaction SMILES: C(N)C1C=CC=CC=1.[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][O:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[C:19]([NH2:28])=[N:20][C:21]([NH2:27])=[N:22]3)[CH2:11][CH2:10]1.[CH3:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32]Br>>[CH3:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32][N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][O:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[C:19]([NH2:28])=[N:20][C:21]([NH2:27])=[N:22]3)[CH2:11][CH2:10]1
Reactant: Nc1nc(N)c2c(OCC3CCNCC3)cccc2n1
Reactant: Cc1ccccc1CBr
Solvent: NCc1ccccc1
Product: Cc1ccccc1CN1CCC(COc2cccc3nc(N)nc(N)c23)CC1
Yield: 89 %

Procedure:
The benzylamine was obtained by reacting 5-(piperidin-4-ylmethoxy)quinazoline-2,4-diamine (75 mg; 0.27 mmol) and 2-methylbenzyl bromide (65 mg; 0.35 mmol) via Method BB to yield 91 mg. (89% yield). 1HNMR (400 MHz, DMSO-d6) δ 7.34 (t, J=8.0 Hz, 1H), 7.21 (m, 3H), 7.14 (m, 3H), 6.76 (d, J=8.0 Hz, 1H), 6.52 (d, J=8.4, 11H), 5.94 (br s, 2H), 3.98 (d, J=6.4 Hz, 2H), 3.41 (s, 3H), 2.83 (br, d, J=11.6 Hz, 2H), 2.32 (s, 3H), 2.00 (t, J=10.4 Hz, 2H), 1.9 (m, 1H), 1.73 (d, J=12.8 Hz, 2H), 1.31 (m, 2H). MS m/z (ESI) 378 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][C:12]([C:13]([O:15]C)=[O:14])=[CH:11][C:10]=1[Cl:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCOCC1>[CH2:1]([O:8][C:9]1[C:18]([O:19][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)=[CH:17][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[Cl:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc(Cl)c(OCc2ccccc2)c(OC2CCCCC2)c1
Solvent: C1COCCO1
Product: O=C(O)c1cc(Cl)c(OCc2ccccc2)c(OC2CCCCC2)c1
Yield: 97.6 %

Procedure:
4-(Benzyloxy)-3-chloro-5-(cyclohexyloxy)benzoic acid (4) (329 mg, 97%) was prepared from methyl 4-(benzyloxy)-3-chloro-5-(cyclohexyloxy)benzoate (3) (350 mg, 0.934 mmol) using a procedure essentially the same as in Step (ii) for AAA-001, except that 1,4-dioxane (5 mL) was used instead of THF: m/z 359 [M−H]− (ES−); 1H NMR (400 MHz, DMSO-d6) δ: 13.19 (1H, s), 7.51 (2H, m), 7.48 (2H, m), 7.42-7.33 (3H, m), 5.10 (2H, s), 4.51 (1H, m), 1.94 (2H, m), 1.72 (2H, m), 1.59-1.49 (3H, m), 1.46-1.27 (3H, m).
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([CH2:7][CH3:8])[NH:4][N:3]=1.CS[C:11](=[N:13][C:14](=O)[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[Cl:22])[CH3:12]>O1CCOCC1>[Cl:22][C:16]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:15]=1[C:14]1[N:3]2[N:4]=[C:5]([CH2:7][CH3:8])[CH:6]=[C:2]2[N:1]=[C:11]([CH3:12])[N:13]=1
Reactant: CSC(C)=NC(=O)c1ccc(Cl)cc1Cl
Reactant: CCc1cc(N)n[nH]1
Solvent: C1COCCO1
Product: CCc1cc2nc(C)nc(-c3ccc(Cl)cc3Cl)n2n1
Temperature: 25 °C
Yield: 13.7 %

Procedure:
A mixture of 3-amino-5-ethylpyrazole (10.3 g, 39.3 mmol) and N-(1-(methylthio)ethylidene)-2,4-dichloro-benzamide (4.0 g, 35.7 mmol) in anhydrous dioxan (20 mL) was stirred at reflux temperature under a nitrogen atmosphere for 16 h. After being cooled to ambient temperature, the reaction mix was concentrated in vacuo and the residue was treated with dichloromethane. The resulting supsension was filtered and the filtrate was concentrated in vacuo to afford an oil (1.5 g, 14% yield): NMR (CDCl3,300 MHz): δ 7.62 (d, 1H, J=8), 7.59 (d, 1H, J=2), 7.45 (dd, 1H, J=8,2), 6.42 (s, 1H), 2.82 (q, 2H, J=8), 2.73 (s, 3H), 1.30 (t, 3H, J=8).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[C:9]([CH3:17])([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:10])=[CH:4][CH:3]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:10][C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)([CH3:17])[C:8]([C:5]1[CH:6]=[CH:7][C:2]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:3][CH:4]=1)=[O:18]
Reactant: C1COCCN1
Reactant: CC(C)(C(=O)c1ccc(F)cc1)N1CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C(=O)c1ccc(N2CCOCC2)cc1)N1CCOCC1
Temperature: 160 °C
Reaction time: 18 h

Procedure:
15.08 g (0.06 mol) of 1-(4-fluorophenyl)-2-methyl-2-morpholinopropan-1-one and 5.23 g (0,06 mol) of morpholine are dissolved in 25 ml of dimethyl sulfoxide, and the solution is heated to 160° C. together with 8.3 g (0.06 mol) of potassium carbonate. After 18 hours of stirring at about 160° C. the suspension is cooled down and is poured onto an ice-water mixture. The crystals are filtered off, are washed with water and are recrystallised from ethanol. Melting point 114°-116° C.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[C:10]1[N:17]=[C:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[NH:19][C:20](=[O:21])[C:9]1=[CH:8]2.I[CH3:28]>CN(C)C=O>[CH3:28][N:19]1[C:20](=[O:21])[C:9]2[C:10](=[N:11][C:12]3[C:7]([CH:8]=2)=[CH:6][C:5]([O:4][CH3:3])=[C:14]([O:15][CH3:16])[CH:13]=3)[N:17]=[C:18]1[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CI
Reactant: CCOC(=O)c1nc2nc3cc(OC)c(OC)cc3cc2c(=O)[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1nc2nc3cc(OC)c(OC)cc3cc2c(=O)n1C
Temperature: 0 °C

Procedure:
Sodium hydride (470 mg. of 50% in oil, 0.011 mole) is added to a slurry of ethyl 7,8-dimethoxypyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylate (3.3 g., 0.01 mole) in N,N-dimethylformamide (75 ml.). The mixture is stirred and heated on a steambath for ten minutes and then at room temperature for a half hour. It is cooled in an ice-bath and iodomethane (2.1 g., 0.015 mole) added dropwise over a 30 minute period. Following completion of addition, the mixture is stirred for an additional 15 minutes in an ice-bath and then for a half-hour at room temperature. The reaction mixture is poured into ice-water (200 ml.) and the resulting solid filtered off, air-dried, and recrystallized from ethanol to give 2.1 g. of yellow crystals (61.2%); m.p. 211.5° C. (dec.)
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N+:3]=1[O-:8].[N+:9]([O-])([OH:11])=[O:10]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:4][N+:3]=1[O-:8]
Reactant: [O-][n+]1ccccc1Br
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=[N+]([O-])c1cc[n+]([O-])c(Br)c1
Temperature: 25 °C
Yield: 63 %

Procedure:
2-Bromopyridine-N-oxide (28.36 g) was carefully dissolved in concentrated sulphuric acid (43 ml) with stirring. A mixture of concentrated sulphuric acid (65 ml) and concentrated nitric acid (43 ml) was added dropwise, and the mixture refluxed for 3 hours and allowed to cool to room temperature. The mixture was then poured on to ice and the precipitate removed by filtration , washed with water and air dried leaving a fine yellow powder of 2-Bromo-4-nitro-pyridine-N-oxide (14.08 g, 63%), m.p. 145-147° C.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH:9]([NH2:14])[CH2:8]2)([O-:4])=[O:3].C(N(CC)CC)C.[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C>[ClH:1].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH:9]([NH:14][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:8]2)([O-:4])=[O:3]
Reactant: NC1Cc2ccc([N+](=O)[O-])cc2C1
Reactant: BrCc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc2c(c1)CC(NCc1ccccc1)C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 5-nitro-2-aminoindane hydrochloride (3.00 g, 14.00 mmol) in DMF (60 ml) was added triethylamine (4.07 ml, 29.40 mmol) followed by benzyl bromide (1.74 ml, 14.68 mmol). The mixture was warmed to room temperature, stirred for 1 hr, dumped into water (200 ml), and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with water, dried over magnesium sulfate, filtered through a small plug of silica gel and reduced to a syrup. The sub-titled compound was isolated as the hydrochloride salt: (2.29 g, 54%); m.p. dec 266° C.
Reaction SMILES: CS(O[CH:6]([C:15]1[CH:16]=[N:17][C:18]([NH:21][C:22]([C:24]2([C:27]3[CH:35]=[CH:34][C:30]4[O:31][CH2:32][O:33][C:29]=4[CH:28]=3)[CH2:26][CH2:25]2)=[O:23])=[CH:19][CH:20]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14])(=O)=O.C[O:37][CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.O1C2C=CC(C3(C(NC4C=CC(C(N(C)C)C5C=CC=CC=5OC)=CN=4)=O)CC3)=CC=2OC1>>[O:31]1[C:30]2[CH:34]=[CH:35][C:27]([C:24]3([C:22]([NH:21][C:18]4[CH:19]=[CH:20][C:15]([CH:6]([N:43]5[CH2:44][CH2:45][N:40]([CH2:39][CH2:38][OH:37])[CH2:41][CH2:42]5)[C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=5[O:13][CH3:14])=[CH:16][N:17]=4)=[O:23])[CH2:25][CH2:26]3)=[CH:28][C:29]=2[O:33][CH2:32]1
Reactant: COCCN1CCNCC1
Reactant: COc1ccccc1C(OS(C)(=O)=O)c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1
Agent: COc1ccccc1C(c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1)N(C)C
Product: COc1ccccc1C(c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1)N1CCN(CCO)CC1

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((4-(2-hydroxyethyl)piperazin-1-yl)(2-methoxyphenyl)methyl)pyridin-2-yl)cyclopropanecarboxamide was prepared from (6-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)pyridin-3-yl)(2-methoxyphenyl)methyl methanesulfonate and 1-(2-methoxyethyl)piperazine in a manner analogous to that of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((dimethylamino)(2-methoxyphenyl)methyl)pyridin-2-yl)cyclopropanecarboxamide.
Reaction SMILES: O.[C:2]1([OH:10])[CH:9]=[C:7]([CH3:8])[CH:6]=[C:4]([OH:5])[CH:3]=1.[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19](Cl)(=[O:21])=[O:20])#[N:12].C(OCC)C>C([O-])(O)=O.[Na+].O>[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19]([O:5][C:4]1[CH:3]=[C:2]([OH:10])[CH:9]=[C:7]([CH3:8])[CH:6]=1)(=[O:21])=[O:20])#[N:12]
Reactant: Cc1cc(O)cc(O)c1
Reactant: N#Cc1ccccc1S(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: Cc1cc(O)cc(OS(=O)(=O)c2ccccc2C#N)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57 %

Procedure:
Orcinol monohydrate (1.42 g, 10.0 mmol) and 2-cyanobenzenesulfonyl chloride 2.02 g, 10.0 mmol) were mixed in saturated NaHCO3 (30 mL) and diethyl ether 30 mL). The biphasic mixture was stirred vigorously at room temperature overnight. The reaction mixture was diluted with water (50 mL) and extracted into ethyl acetate (3×50 mL). The organic phase was washed with brine (2×50 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography (dichloromethane to 5% ethyl acetate in dichloromethane) to give the title compound as a white solid (1.65 g, 57%). 1H-NMR (300 MHz, CDCl3) δ8.07 (m, 1H), 7.94 (m, 1H), 7.75-7.80 (m, 2H), 6.57 (s, 1H), 6.53 (s, 1H), 6.49 (s, 1H), 5,69 (br s, 1H), 2.22 (s, 3H).
Reaction SMILES: C(=O)(O)[O-].[Na+].Cl.[NH2:7][CH2:8][C:9]#[C:10][CH2:11][OH:12].[CH:13]1([CH3:25])[CH2:18][CH2:17][CH:16]([CH:19]([CH3:21])[CH3:20])[CH:15]([C:22](Cl)=[O:23])[CH2:14]1>O.CCOCC>[OH:12][CH2:11][C:10]#[C:9][CH2:8][NH:7][C:22]([CH:15]1[CH:16]([CH:19]([CH3:21])[CH3:20])[CH2:17][CH2:18][CH:13]([CH3:25])[CH2:14]1)=[O:23]
Reactant: NCC#CCO
Reactant: CC1CCC(C(C)C)C(C(=O)Cl)C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: CC1CCC(C(C)C)C(C(=O)NCC#CCO)C1
Reaction time: 2 h

Procedure:
Sodium bicarbonate (2.5 g.) and 4-aminobut-2-yn-1-ol hydrochloride (2.5 g.) were dissolved in water (60 ml.) and a solution of p-menth-3-oyl chloride in ether (100 ml.) added. The mixture was stirred vigorously for two hours and the ether layer separated and dried over MgSO4. Evaporation of the ether gave N-(4-hydroxybut-2-ynyl)-p-menthane-3-carboxamide as a very viscous liquid: b.p. 180°/0.1 mm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23](O)=[O:24].Cl.[O:38]1[C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=[N:39]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:23]([NH:44][CH2:43][C:42]1[O:38][N:39]=[CH:40][CH:41]=1)=[O:24]
Reactant: NCc1ccno1
Reactant: COc1ccc(CC2c3cc(OC)c(OC)cc3CCCN2C(C(=O)O)c2ccccc2)cc1OC
Agent: Cl
Product: COc1ccc(CC2c3cc(OC)c(OC)cc3CCCN2C(C(=O)NCc2ccno2)c2ccccc2)cc1OC

Procedure:
prepared by reaction of [1-(3,4-dimethoxy-benzyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl]-phenyl-acetic acid with C-isoxazol-5-yl-methylamine hydrochloride.
Reaction SMILES: [N:1](=[C:3]1[C:7](=[N:8][OH:9])[CH2:6][O:5][C:4]1=[O:10])[OH:2].[CH:11]([NH2:14])([CH3:13])[CH3:12]>CO>[OH:5][CH2:6][C:7](=[N:8][OH:9])[C:3](=[N:1][OH:2])[C:4]([NH:14][CH:11]([CH3:13])[CH3:12])=[O:10]
Reactant: CC(C)N
Reactant: O=C1OCC(=NO)C1=NO
Solvent: CO
Product: CC(C)NC(=O)C(=NO)C(CO)=NO
Reaction time: 3 h

Procedure:
9.4 g of 3,4-dioximino-2-oxotetrahydrofuran are suspended in 50 ml of methanol, and 4.2 g of isopropylamine are added. The mixture is stirred for 3 h and then cooled in an ice bath. The solid material is filtered off with suction and recrystallized from methanol.
Reaction SMILES: [C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[CH3:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=1[CH3:14].[Cl-].[Al+3].[Cl-].[Cl-].Cl>O>[CH3:7][C:8]1[CH:9]=[C:10]([C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])[CH:11]=[CH:12][C:13]=1[CH3:14]
Reactant: Cc1ccccc1C
Reactant: CC(C)C(=O)Cl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Product: Cc1ccc(C(=O)C(C)C)cc1C
Temperature: 2.5 °C
Reaction time: 3 h

Procedure:
In a nitrogen atmosphere, 213.1 g (2.0 mol) of isobutyryl chloride and 400 g of o-xylene are introduced into a 1.5 litre reaction flask. The solution is cooled to 5-0° C. Then, over about three hours, 293.3 g (2.2 mol) of aluminium chloride are added in small portions at 0-5° C. After the evolution of HCl gas has ceased, the reaction is checked using GC. The dark-red reaction solution is then poured into ice and water and stirred to complete the reaction. The two phases are separated in a separating funnel. The organic phase is washed with water and is then concentrated using a vacuum rotary evaporator. The last remnants of solvent are removed under a high vacuum. 329.1 g of faintly yellowish oil remain behind. The product is checked using GC and a 1H NMR spectrum. The product, 1-(3,4-dimethyl-phenyl)-2-methyl-propan-1-one, is used directly in the next reaction.
Reaction SMILES: [CH3:1][S-:2].[Na+].F[C:5]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([C:19]([F:22])([F:21])[F:20])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8].O.[OH-].[Li+].Cl>C1(C)C(C)=CC=CC=1>[CH3:18][O:17][C:15]([C:14]1[C:5]([S:2][CH3:1])=[C:6]([CH:11]=[CH:12][C:13]=1[C:19]([F:22])([F:21])[F:20])[C:7]([O:9][CH3:10])=[O:8])=[O:16]
Reactant: C[S-]
Reactant: COC(=O)c1ccc(C(F)(F)F)c(C(=O)OC)c1F
Agent: Cl
Agent: [Li+]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1C
Product: COC(=O)c1ccc(C(F)(F)F)c(C(=O)OC)c1SC
Reaction time: 48 h
Yield: 50.1 %

Procedure:
Sodium thiomethoxide (6.83 g) was added to a solution of methyl 2-fluoro-3-methoxycarbonyl-4-trifluoromethylbenzoate (24.85 g) in xylene. After stirring for 0.5 hours lithium hydroxide monohydrate (4.10 g) was added and the mixture was stirred for 48 hours. Hydrochloric acid (2M) was added. It was extracted with ether, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane. The solid was filtered off and the filtrate was evaporated to dryness to give methyl 3-methoxycarbonyl-2-(methylsulphenyl)-4-trifluoromethylbenzoate (13.71 g) as a yellow oil NMR (CDCl3) 2.4(s,3H), 3.95 (s,6H), 7.65 (s,2H).