Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1CCO[CH:2]1[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:16]=[CH:15][NH:14][N:13]=2)[N:7]=1>C(Cl)(Cl)Cl.CO>[NH:14]1[CH:15]=[CH:16][C:12]([C:8]2[N:7]=[C:6]([CH:2]=[O:1])[CH:11]=[CH:10][CH:9]=2)=[N:13]1
Reactant: c1cc(-c2cc[nH]n2)nc(C2OCCO2)c1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: O=Cc1cccc(-c2cc[nH]n2)n1

Procedure:
The deprotection of the acetal function of 2-[1,3]dioxolan-2-yl-6-(1H-pyrazol-3-yl)pyridine is carried out on 0.65 g of product (2.99 mmol) according to a protocol similar to that used in stage 5 of Example 7. The title compound is isolated by chromatography on a silica column (eluent: chloroform/methanol; 98:2). 0.31 g of a white foam is obtained.
Reaction SMILES: Cl.F[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[N:8][CH:7]=[CH:6]2.[NH2:13][C@@H:14]1[CH2:19][CH2:18][C@H:17]([OH:20])[CH2:16][CH2:15]1>>[CH:9]1[C:10]2[C:5](=[CH:4][C:3]([O:20][C@@H:17]3[CH2:18][CH2:19][C@H:14]([NH2:13])[CH2:15][CH2:16]3)=[CH:12][CH:11]=2)[CH:6]=[CH:7][N:8]=1
Reactant: N[C@H]1CC[C@@H](O)CC1
Reactant: Fc1ccc2cnccc2c1
Agent: Cl
Product: N[C@H]1CC[C@@H](Oc2ccc3cnccc3c2)CC1

Procedure:
Starting from 6-fluoro-isoquinoline hydrochloride and cis-4-amino-cyclohexanol the title compound was prepared following the protocol described for compound (15). Rt=0.64 min (Method B). Detected mass: 243.2 (M+H+).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][C@H:16]([C:20]([OH:22])=O)[CH:17]([CH3:19])[CH3:18])(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH:2]=[C:3]=[CH2:4].[OH:23][N:24]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.NO>CN(C)C=O>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][CH:16]([CH:17]([CH3:19])[CH3:18])[C:20]([NH:24][OH:23])=[O:22])(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH:2]=[C:3]=[CH2:4]
Reactant: C=C=CCOc1ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: NO
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: C=C=CCOc1ccc(S(=O)(=O)NC(C(=O)NO)C(C)C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 45.2 %

Procedure:
To a solution of product from Example 12 (210 mg, 0.65 mmol) in dimethylformamide (6 ml) was added 1-hydroxybenzotriazol (105 mg, 0.78 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (173 mg, 0.90 mmol), and N-methylmorpholine (0.106 mmol, 0.97 mmol) and the resulting mixture was stirred for 1 hour at room temperature. A 50% aqueous solution of hydroxylamine (0.119 ml, 1.94 mmol) was added and the mixture was stirred for 15 hours at room temperature. The reaction mixture was concentrated in vacuo, diluted with water, and extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, water, saturated sodium bicarbonate, saturated sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent in vacuo gave 100 mg (45%) of the product.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1)#[N:2].[Br:10][CH2:11][CH2:12][CH2:13]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CCOCC>[Br:10][CH2:11][CH2:12][CH2:13][O:9][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[C:1]#[N:2]
Reactant: N#Cc1cccc(O)c1
Reactant: OCCCBr
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: N#Cc1cccc(OCCCBr)c1
Reaction time: 5 h

Procedure:
3-Cyanophenol (10.0 g, 84 mM), 3-bromopropanol (20.3 mL, 114 mM), triphenylphosphine (29.7 g, 114 mM) were stirred in anhydrous THF (40 mL) at room temperature and treated with diethylazodicarboxylate (17.8 mL, 114 mM) dropwise over 5 min. under an atmosphere of nitrogen. This mixture stirred for about 5 hours then diluted with ether (500 mL) and filtered through Celite™. The filtrate was concentrated to a reddish oil which was again dissolved in ether (250 mL), diluted with hexanes (200 mL) and filtered. The filtrates were concentrated then filtered through a silica pad (300 g) eluting with 35% acetone/hexanes to collect the desired product as a yellow oil, 16.85 g. This material was used in its crude form.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:33])[C:7]=1[NH:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]([O:31][CH3:32])=[C:15]2[O:30][C:18]3[CH2:19][N:20](C(OC(C)(C)C)=O)[CH2:21][CH2:22][C:17]=3[C:16]=12)=[O:10].Cl>C(OCC)(=O)C>[ClH:1].[Cl:33][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[NH:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]([O:31][CH3:32])=[C:15]2[O:30][C:18]3[CH2:19][NH:20][CH2:21][CH2:22][C:17]=3[C:16]=12)=[O:10]
Reactant: COc1ccc(C(=O)Nc2c(Cl)cncc2Cl)c2c3c(oc12)CN(C(=O)OC(C)(C)C)CC3
Agent: Cl
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)Nc2c(Cl)cncc2Cl)c2c3c(oc12)CNCC3

Procedure:
N-(3,5-dichloropyridin-4-yl)-2-(tert-butoxycarbonyl)-8-methoxy-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridine-5-carboxamide (from step 3) (645 mg, 0.0013 mol) was taken in dry ethyl acetate and ethyl acetate saturated with HCl was added to it at 0° C. it was then stirred for an hour. Ethyl acetate was removed under diminished pressure and dry solvent ether was added to it. Solid N-(3,5-dichloropyridin-4-yl)-8-methoxy-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridine-5-carboxamide hydrochloride (XIII) was filtered, washed with dry solvent ether and dried.
Reaction SMILES: Br[C:2]1[S:3][C:4]([Cl:7])=[CH:5][CH:6]=1.OB(O)[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[Cl:7][C:4]1[S:3][CH:2]=[CH:6][C:5]=1[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1
Reactant: Clc1ccc(Br)s1
Reactant: O=C(O)c1ccc(B(O)O)cc1
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: COCCOC
Product: O=C(O)c1ccc(-c2ccsc2Cl)cc1
Temperature: 75 °C
Reaction time: 0.08 h

Procedure:
Solid Pd(PPh3)4 (11.0 mg, 0.01 mmol) was treated with a room temperature solution of 2-bromo-5-chlorothiophene (143 mg, 0.72 mmol) in DME (4 mL), stirred for 5 minutes, treated with a solution of 4-(dihydroxyboryl)benzoic acid (100 mg, 0.60 mmol) in DME (2 mL), and stirred for 5 minutes. The mixture was treated with 2M Na2CO3 (1.5 mL, 3.0 mmol), heated to 75° C., stirred for 18 hours, cooled to room temperature, filtered, triturated with water (3 mL), and concentrated. The concentrate was treated with boiling water (4 mL), filtered through celite, cooled to room temperature, adjusted to pH<7 with HCl, and filtered to provide the desired product. MS (APCI(+)) m/e 239 (M+H)+.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[C@:8]12[CH2:16][C@H:15]1[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)=[O:4].O.[OH-].[Li+]>CO>[F:23][C:20]1[CH:19]=[CH:18][C:17]([C@@H:15]2[C@:8]3([C:7]4[C:11](=[CH:12][CH:13]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=4)[NH:10][C:9]3=[O:14])[CH2:16]2)=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc2c(c1)[C@]1(C[C@H]1c1ccc(F)cc1)C(=O)N2
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1ccc2c(c1)[C@@]1(C[C@@H]1c1ccc(F)cc1)C(=O)N2
Temperature: 25 °C
Reaction time: 14 h
Yield: 39.3 %

Procedure:
To a solution of (1S,2R) and (1R,2S)-methyl-2-(4-fluorophenyl)-2′-oxospiro [cyclopropane-1,3′-indoline]-5′-carboxylate (80 mg) in methanol (1 mL); water (0.1 mL) was added lithium hydroxide (10 mg) at room temperature. The mixture was stirred for 14 hours at room temperature. HPLC monitored the reaction finished. The solvent was removed under reduced pressure. The residue was dissolved in 2 mL of DMF. Purification by preparative HPLC gave the title compound as white solid (30 mg). LC/MS m/e calcd. for C17H12FNO3 297, observed (M−H)+: 296. 1HNMR (400 MHz, DMSO-d6) δppm 1.99 (dd, J=9.09, 4.80 Hz, 1 H) 2.35 (dd, J=8.08, 4.80 Hz, 1 H), 3.11 (t, J=8.46 Hz, 1 H) 6.65 (d, J=1.52 Hz, 1 H) 6.94 (d, J=8.08 Hz, 1 H) 7.14 (t, J=8.84 Hz, 2 H) 7.34 (dd, J=8.34, 5.56 Hz, 2 H) 7.72 (dd, J=8.08, 1.52 Hz, 1 H) 10.97 (s, 1 H) 12.36 (br. s., 1 H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:32]C(=O)OC(C)(C)C)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[NH:24][CH:25]=[C:26]([NH:27][C:28](=[O:31])[CH2:29][OH:30])[C:19]=34)[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C(Cl)Cl>[NH2:32][C@H:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C:10]([N:12]1[CH2:13][CH2:14][N:15]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[NH:24][CH:25]=[C:26]([NH:27][C:28](=[O:31])[CH2:29][OH:30])[C:19]=23)[CH2:16][CH2:17]1)=[O:11]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2ccnc3[nH]cc(NC(=O)CO)c23)CC1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2ccnc3[nH]cc(NC(=O)CO)c23)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.2 %

Procedure:
(R)-tert-Butyl 3-(4-chlorophenyl)-1-(4-(3-(2-hydroxyacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (0.040 g, 0.072 mmol) was placed in DCM (3 mL) at room temperature. TFA (0.5 mL) was then added, and the reaction was stirred at room temperature for 1 hour. The reaction was then concentrated to dryness, and the resulting residue was dissolved in minimal DCM. The solution was added dropwise to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether, and dried to give (R)—N-(4-(4-(2-amino-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxyacetamide (0.030 g, 79% yield) as the dihydrochloride salt. MS APCI (+) m/z 457 detected.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([CH:9]=[CH2:10])[C:6]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:5]([F:16])[CH:4]=1.[C:17]([C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[C:28]([CH3:32])[C:29](O)=[O:30])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18].CCOC(OC(OCC)=O)=O>CN(C=O)C>[C:17]([C:21]1[CH:22]=[CH:23][C:24]([CH:27]=[C:28]([CH3:32])[C:29]([NH:1][CH2:2][C:3]2[CH:8]=[C:7]([CH:9]=[CH2:10])[C:6]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:5]([F:16])[CH:4]=2)=[O:30])=[CH:25][CH:26]=1)([CH3:20])([CH3:18])[CH3:19]
Reactant: C=Cc1cc(CN)cc(F)c1NS(C)(=O)=O
Reactant: CC(=Cc1ccc(C(C)(C)C)cc1)C(=O)O
Agent: CCOC(=O)OC(=O)OCC
Solvent: CN(C)C=O
Product: C=Cc1cc(CNC(=O)C(C)=Cc2ccc(C(C)(C)C)cc2)cc(F)c1NS(C)(=O)=O
Reaction time: 12 h
Yield: 55.9 %

Procedure:
N-(4-Aminomethyl-2-fluoro-6-vinylphenyl)methanesulfonamide (0.15 mmol, 54.21 mg), 3-(4-tert-butyl-phenyl)-2-methylacrylic acid (0.14 mmol, 30 mg), DEPC (1.2 eq, 0.17 mmol, 25.49 μl), and TEA (2 eq, 0.28 mmol, 39.03 μl) were added in DMF. The reaction mixture was stirred for 12 hrs. The reaction mixture was purified according to similar procedure of Example 21 to yield title product (34.8 mg, 55.96%).
Reaction SMILES: [C:1]1([C:7]2[CH:25]=[C:24]3[C:10]([C:11](=[O:27])[C:12](=[O:26])[C:13]4[S:23][CH2:22][C:16]5([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]5)[O:15][C:14]=43)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1>>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:19]2[CH2:20][CH2:21][C:16]3([O:15][C:14]4[C:24]5[C:10]([C:11](=[O:27])[C:12](=[O:26])[C:13]=4[S:23][CH2:22]3)=[CH:9][CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:25]=5)[CH2:17][CH2:18]2)=[CH:31][CH:32]=1
Reactant: O=C1C(=O)c2ccc(-c3ccccc3)cc2C2=C1SCC1(CCNCC1)O2
Reactant: Fc1ccc(CBr)cc1
Product: O=C1C(=O)c2ccc(-c3ccccc3)cc2C2=C1SCC1(CCN(Cc3ccc(F)cc3)CC1)O2

Procedure:
Compound 148 was synthesized using 9-phenylspiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione and 1-(bromomethyl)-4-fluorobenzene and conditions outlined in procedure V. M.p.=197-198° C.; 400 MHz 1H NMR (DMSO-d6) δ: 7.95 (m, 2H), 7.87 (d, J=7.6 Hz, 1H), 7.74 (d, J=6.8 Hz, 2H), 7.60 (m, 2H), 7.52 (m, 1H), 7.34 (m, 2H), 7.10 (t, J=8 Hz, m, 2H), 3.5 (s, 2H), 3.10 (s, 2H), 2.71 (m, 2H), 2.39 (m, 2H), 2.03 (m, 2H), 1.84 (m, 2H); LCMS: 486 [M+H].
Reaction SMILES: C([S:9][CH:10]([CH3:26])[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15][CH:14]1[C:23]([OH:25])=[O:24])=[O:12])(=O)C1C=CC=CC=1.[OH-].[NH4+]>O>[SH:9][CH:10]([CH3:26])[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15][CH:14]1[C:23]([OH:25])=[O:24])=[O:12]
Reactant: CC(SC(=O)c1ccccc1)C(=O)N1c2ccccc2CCC1C(=O)O
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: CC(S)C(=O)N1c2ccccc2CCC1C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
(±)-1-(2-Benzoylthio-1-oxopropyl)-1,2,3,4-tetrahydro-2-quinolinecarboxylic acid (4.5 g), concentrated ammonium hydroxide (8 ml) and water (16 ml) were combined and stirred at room temperature under nitrogen for three hours. The benzamide was filtered and the filtrate diluted with water (25 ml). The reaction mixture was then extracted with ethyl acetate and acidified with concentrated hydrochloric acid. The product was extracted with chloroform and the chloroform extracts dried over sodium sulfate and activated charcoal, and concentrated in vacuo. The residue, (±)-1-(2-mercapto-1-oxopropyl)-1,2,3,4-tetrahydro-2-quinolinecarboxylic acid, was triturated with carbon tetrachloride (20 ml); yield 3.2 g, m.p. 141°-143°.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][C:14]=2[O:15][CH:16]([F:18])[F:17])[C:9](Cl)=[O:10])[CH2:3][CH2:2]1.[Cl:19][C:20]1[CH:21]=[N:22][CH:23]=[C:24]([Cl:39])[C:25]=1[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1)=[O:28]>>[Cl:39][C:24]1[CH:23]=[N:22][CH:21]=[C:20]([Cl:19])[C:25]=1/[CH:26]=[C:27](\[O:28][C:9](=[O:10])[C:8]1[CH:12]=[CH:13][C:14]([O:15][CH:16]([F:18])[F:17])=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[CH:7]=1)/[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1
Reactant: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)cc1OC
Reactant: O=C(Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
Product: COc1ccc(/C(=C/c2c(Cl)cncc2Cl)OC(=O)c2ccc(OC(F)F)c(OCC3CC3)c2)cc1OC

Procedure:
The compound was obtained starting from 3-cyclopropylmethoxy-4-difluoromethoxy -benzoyl chloride and 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy -phenyl)-ethanone, following the procedure of Example 7.
Reaction SMILES: ClC1C=CC(B(O)O)=CC=1.BrC1N=CNC=1.Br[C:18]1[N:19]=[CH:20][N:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[CH:22]=1.[O:30]1[CH:34]=[CH:33][CH:32]=[C:31]1B(O)O>>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([N:21]2[CH:22]=[C:18]([C:31]3[O:30][CH:34]=[CH:33][CH:32]=3)[N:19]=[CH:20]2)=[CH:24][CH:25]=1
Reactant: OB(O)c1ccco1
Reactant: Clc1ccc(-n2cnc(Br)c2)cc1
Agent: Brc1c[nH]cn1
Agent: OB(O)c1ccc(Cl)cc1
Product: Clc1ccc(-n2cnc(-c3ccco3)c2)cc1
Yield: 12 %

Procedure:
The procedure described above for Formula Ic-iii in Example 16 was followed, starting from 4-chloro-phenylboronic acid and 4-bromo-1H-imidazole, to prepare 4-bromo-1-(4-chlorophenyl)-1H-imidazole, which was then reacted with furan-2-ylboronic acid to prepare the desired 1-(4-chlorophenyl)-4-(furan-2-yl)-1H-imidazole (15 mg, 0.061 mmol, yield 12%) as an off-white solid. The HPLC purity of the final product was 95.45%. LC-MS [M+H] 245 (C13H9ClN2O+H expected 245.04). The 1H-NMR spectra was in accordance with the chemical structure.
Reaction SMILES: CC1C=CC(S(OCCC2C=CC=C3C=2NN=C3S(C2C=CC=CC=2)(=O)=O)(=O)=O)=CC=1.[C:32]1([S:38]([C:41]2[C:49]3[C:44](=[C:45]([CH2:50][CH2:51]O)[CH:46]=[CH:47][CH:48]=3)[NH:43][N:42]=2)(=[O:40])=[O:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[N:53]1[CH:58]=CC=C[CH:54]=1.C1(C)C(S([Cl:68])(=O)=O)=CC=CC=1>ClCCl>[ClH:68].[CH3:54][N:53]([CH3:58])[CH2:51][CH2:50][C:45]1[CH:46]=[CH:47][CH:48]=[C:49]2[C:44]=1[NH:43][N:42]=[C:41]2[S:38]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)(=[O:40])=[O:39]
Reactant: O=S(=O)(c1ccccc1)c1n[nH]c2c(CCO)cccc12
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: c1ccncc1
Agent: Cc1ccc(S(=O)(=O)OCCc2cccc3c(S(=O)(=O)c4ccccc4)n[nH]c23)cc1
Solvent: ClCCl
Product: CN(C)CCc1cccc2c(S(=O)(=O)c3ccccc3)n[nH]c12
Product: Cl
Temperature: 25 °C
Reaction time: 12 h
Yield: 93 %

Procedure:
2-[3-(Phenylsulfonyl)-1H-indazol-7-yl]ethyl 4-methylbenzenesulfonate To a solution of 2-[3-(phenylsulfonyl)-1H-indazol-7-yl]ethanol (0.64 g, 2.12 mmol) in anhydrous dichloromethane (30 mL) at 0° C. was added pyridine (0.43 mL) and toluenesulfonyl chloride (0.475 g, 2.5 mmol). The solution was stirred for 12 hours at room temperature. The mixture was concentrated in vacuo and taken up in ethyl acetate (30 mL). The organic layer was washed with 2 M HCl, (2×25 mL), brine, dried (MgSO4), filtered and concentrated under reduced pressure. Silica gel chromatography (50% ethyl acetate/petroleum ether) gave the title compound as a white foam (0.9 g, 93%). Mp: 61-64° C. MS (ES−): 455 (M−H) Step 7
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2(C#N)[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+]>Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:12])[CH2:16][CH2:17]2)=[N:6][CH:7]=1
Reactant: N#CC1(c2ccc(Br)cn2)CCC2(CC1)OCCO2
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=C1CCC(c2ccc(Br)cn2)CC1
Yield: 10.8 %

Procedure:
8-(5-Bromopyridin-2-yl)-1,4-dioxaspiro[4,5]decane-8-carbonitrile (1 g) described in Reference Example 82 was stirred in concentrated hydrochloric acid (5 ml) at 100° C. for eight hours. After completion of the reaction, the reaction solution was made alkaline by the addition of a saturated aqueous solution of potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to give the titled compound (85 mg) as a white solid.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:12]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][C:39]3[S:40][C:41]([C:44]4[O:45][CH:46]=[CH:47][CH:48]=4)=[CH:42][N:43]=3)[CH:32]=2)[O:11][C@@H:10]1[C:49]([OH:51])=[O:50])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si](C=[N+]=[N-])(C)(C)[CH3:53].O>C(Cl)Cl>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@H:12]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][C:39]3[S:40][C:41]([C:44]4[O:45][CH:46]=[CH:47][CH:48]=4)=[CH:42][N:43]=3)[CH:32]=2)[O:11][C@@H:10]1[C:49]([O:51][CH3:53])=[O:50])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ncc(-c4ccco4)s3)c2)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Solvent: O
Solvent: ClCCl
Product: COC(=O)[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ncc(-c4ccco4)s3)c2)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 32.4 %

Procedure:
To the solution of acid 104 (1.7 g, 2.35 mmol) in CH2Cl2 (7.8 mL) was added TMSCHN2 (1.4 mL, 2.82 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 15 h. H2O was added to the reaction mixture and then extracted with CH2Cl2. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification by silica gel column chromatography provided the desired methyl ester 105 (560 mg, 32%) as a solid. MH+737.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[CH:6]1.[F:14][C:15]1[CH:16]=[C:17]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:18]=[CH:19][CH:20]=1.C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[F:14][C:15]1[CH:16]=[C:17]([N:21]2[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH2:4][N:5]3[C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[N:7]=[CH:6]3)[CH2:23][CH2:22]2)[CH:18]=[CH:19][CH:20]=1
Reactant: ClCCCn1cnc2ccccc21
Reactant: Fc1cccc(N2CCNCC2)c1
Agent: [I-]
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: Fc1cccc(N2CCN(CCCn3cnc4ccccc43)CC2)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 63 %

Procedure:
1-(3-chloropropyl)-1H-benzimidazole (6.98 g, 0.036 mol) was dissolved into 100 ml of acetonitrile, 3-fluorophenyl piperazine (6.91 g, 0.03 mol), diisopropylethylamine (15.5 g, 0.12 mol) and potassium iodide (5.0 g, 0.03 mol) were respectively added. The mixture was stirred for 10 min at ambient temperature, and then heated and refluxed to react for 10-15 hours. The mixture was cooled down to ambient temperature and filtered. The filtrate was concentrated to produce oily products, and treated by chromatography with neutral Al2O3, eluted with dichloromethane/methanol mixture to produce 6.4 g compound (I-8) with a yield of 63.1%. ESI-MS [M+H]+: m/z 339.2.
Reaction SMILES: Br[C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:9](=[N:22][NH2:23])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[C:10]1([C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:22][NH:23][C:2]2[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: NN=C(c1ccccc1)c1ccccc1
Reactant: Cc1ncccc1Br
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Cc1ncccc1NN=C(c1ccccc1)c1ccccc1
Temperature: 120 °C
Yield: 75 %

Procedure:
3-Bromo-2-methyl-pyridine (1.0 g, 5.80 mmol) in 15 mL dry toluene was treated with benzophenone hydrazone (1.25 g, 6.39 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (170 mg, 0.29 mmol), sodium tert-butoxide (835 mg, 8.70 mmol), and Pd(II)(OAc)2 (67 mg, 0.30 mmol). Heated to 120° C. in the microwave for five minutes. Extracted using EtOAc/H2O (3×100 mL EtOAc, 1×100 mL H2O, 1×100 mL brine). Dried using Na2SO4 and then purified by flash chromatography (silica, 10-50% EtOAc/Hexane) to afford 3-(2-(diphenylmethylene)hydrazinyl)-2-methylpyridine (1.25 g, 4.35 mmol, 75%). 1H NMR (300 MHz, DMSO-d6) δ 7.95 (d, 1H), 7.85 (d, 1H), 7.70-7.53 (m, 6H), 7.45-7.34 (m, 5H), 7.20 (d, 1H), 2.07 (s, 3H); LC-MS (ESI) m/z 288 (M+H)+.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:9]([CH2:10][C:11]([OH:13])=O)=[CH:8][CH:7]=[CH:6][C:5]=12.[Br:14][C:15]1[C:16]([C:21]2[NH:25][N:24]=[CH:23][N:22]=2)=[C:17]([NH2:20])[S:18][CH:19]=1>>[Br:14][C:15]1[C:16]([C:21]2[NH:25][N:24]=[CH:23][N:22]=2)=[C:17]([NH:20][C:11](=[O:13])[CH2:10][C:9]2[N:4]3[CH:3]=[CH:2][N:1]=[C:5]3[CH:6]=[CH:7][CH:8]=2)[S:18][CH:19]=1
Reactant: Nc1scc(Br)c1-c1ncn[nH]1
Reactant: O=C(O)Cc1cccc2nccn12
Product: O=C(Cc1cccc2nccn12)Nc1scc(Br)c1-c1ncn[nH]1

Procedure:
N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(imidazo[1,2-a]pyridin-5-yl)acetamide was synthesized from 2-(imidazo[1,2-a]pyridin-5-yl)acetic acid and 4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-amine according to protocol A. Retention time (min)=7.958, method [6], MS (ESI) 403.0 (M+H); 1H NMR (300 MHz, CD3OD) δ 8.46 (b s, 1H), 8.35 (d, J=2.2 Hz, 1H), 8.12 (d, J=2.2 Hz, 1H), 8.08-7.96 (m, 2H), 7.58 (d, J=7.2 Hz, 1H), 7.16 (s, 1H), 4.64 (s, 2H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:6])[O:4]C.[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Al+3].[Cl-].[Cl-].[Cl-]>>[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:7]1([CH2:1][O:2][C:3](=[O:6])[O-:4])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: COC(=O)OC
Agent: [Al+3]
Agent: [Cl-]
Solvent: Oc1ccccc1
Product: O=C([O-])OCc1ccccc1

Procedure:
The reaction between dimethylcarbonate (DMC) and phenol (phen) was carried out in the presence of anhydrous AlCl3 in the molar ratio DMC/phen/cat=5/1/0.05. The temperature was 98° C., the methyl alcohol -DMC azeotrope was distilled at a reflux ratio of 10:1. After 8 hours obtained a phenol conversion equal 15.5% at a Ph MC selectivity of 95% (Ph MC=phenylmethylcarbonate), the remaining 5% of phenol being converted to anisole.