Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][C:10]([C:16]#[N:17])=[C:9]2Cl)=[O:5])[CH3:2].[N:19]1[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>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>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][C:10]([C:16]#[N:17])=[C:9]2[C:21]1[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=1)=[O:5])[CH3:2]
Reactant: OB(O)c1cccnc1
Reactant: CCOC(=O)c1ccc2ncc(C#N)c(Cl)c2c1
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+]
Product: CCOC(=O)c1ccc2ncc(C#N)c(-c3cccnc3)c2c1

Procedure:
Similar procedure as described in example 61g was used, starting from 4-chloro-3-cyano-quinoline-6-carboxylic acid ethyl ester (example 46c), pyridine-3-boronic acid, tetrakis(triphenylphosphine)palladium(0), and sodium carbonate solution to give 3-cyano-4-pyridin-3-yl-quinoline-6-carboxylic acid ethyl ester. LC-MS m/e 304 (MH+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[N:15][C:16](=S)[C:17]([F:20])([F:19])[F:18])=[CH:4][CH:3]=1.[CH3:22][NH2:23]>CO.C(=O)([O-])[O-].[Ag+2]>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[N:15][C:16](=[N:23][CH3:22])[C:17]([F:20])([F:19])[F:18])=[CH:4][CH:3]=1
Reactant: FC(F)(F)C(=S)N=c1ccccn1Cc1ccc(Cl)nc1
Reactant: CN
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: CO
Product: CN=C(N=c1ccccn1Cc1ccc(Cl)nc1)C(F)(F)F
Temperature: 50 °C
Reaction time: 1 h
Yield: 56 %

Procedure:
150 mg (0.45 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (1-20) synthesized by the method in Synthetic Example 4 was dissolved in 5 ml of methanol, 105 μl (42 mg, 1.36 mmol) of methylamine (40% methanol solution) and 124 mg (0.45 mmol) of silver carbonate were added thereto, and the resulting mixture was stirred at 50° C. for 1 hour. After the reaction was completed, the reaction solution was returned to room temperature and subjected to suction filtration by using celite to remove insoluble materials. Ethyl acetate and water were added thereto to perform liquid separation, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure and purified with silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain the subject material. Amount obtained 81 mg (yield 56%).
Reaction SMILES: C[O:2][CH:3](OC)[C:4]1[CH:5]=[C:6]([S:13][C:14]2[CH:15]=[C:16]([NH:20][S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11].O>Cl.C1COCC1>[CH:3]([C:4]1[CH:5]=[C:6]([S:13][C:14]2[CH:15]=[C:16]([NH:20][S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])=[O:2]
Reactant: COC(OC)c1cc(Sc2cccc(NS(=O)(=O)c3ccccc3)c2)ccc1[N+](=O)[O-]
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1cc(Sc2cccc(NS(=O)(=O)c3ccccc3)c2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of N-[3-(3-dimethoxymethyl-4-nitro-phenylsulfanyl)-phenyl]-benzenesulfonamide (0.027 mol) in 12N HCl (25 mL), THF (75 mL), and water (50 mL) was stirred overnight at room temperature, and then the mixture was extracted with EtOAc. The extract was washed with H2O and then with a saturated Na2CO3 solution. The solvent was evaporated, and the residue was purified by column chromatography over silica gel (eluent: CH2Cl2). The product fractions were collected and the solvent was evaporated to yield the title compound as a residue.
Reaction SMILES: [N:1]([C:4]1[CH:17]=[CH:16][C:7]([C:8]([NH:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[O:9])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].O=[C:19]([CH2:26][CH:27]=[CH2:28])[CH2:20][C:21]([O:23]CC)=[O:22].[O-]CC.[Na+]>C(O)C>[CH:26](/[C:19]1[N:1]([C:4]2[CH:5]=[CH:6][C:7]([C:8]([NH:10][CH2:11][C:12]([F:14])([F:13])[F:15])=[O:9])=[CH:16][CH:17]=2)[N:2]=[N:3][C:20]=1[C:21]([OH:23])=[O:22])=[CH:27]\[CH3:28]
Reactant: [N-]=[N+]=Nc1ccc(C(=O)NCC(F)(F)F)cc1
Reactant: C=CCC(=O)CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: C/C=C/c1c(C(=O)O)nnn1-c1ccc(C(=O)NCC(F)(F)F)cc1

Procedure:
To a solution of 4-azido-N-(2,2,2-trifluoroethyl)benzamide (2.44 g) obtained in Example 46a) in ethanol (40 ml) were added ethyl 3-oxohex-5-enoate (Tetrahedron Lett., 41, 8803-8806 (2000)) (2.10 g) synthesized separately and 20% sodium ethoxide in ethanol solution (4.6 ml), and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was diluted with water and washed with ether. The aqueous layer was acidified with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure to give the title compound as a yellow amorphous substance (1.96 g, 55%).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[C:5]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1)(=[O:7])[CH3:6]>CC(C)=O.O>[C:5]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([S:15]([N:1]=[N+:2]=[N-:3])(=[O:17])=[O:16])=[CH:13][CH:14]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)Nc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.4 %

Procedure:
Sodium azide (7.8 g, 120 mmol) was charged in a 1 L round bottom flask with water. 4-Acetamidobenzene-1-sulfonyl chloride (23.4 g, 100 mmol) was dissolved in acetone, and this solution was slowly added to the solution of sodium azide. The reaction was then stirred for 16 hours at room temperature and diluted with water. The acetone was then removed. The solid was filtered to give 4-acetamidobenzenesulfonyl azide (21 g, 87%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH:8]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[OH:9])=[C:6]([F:16])[C:5]([C@H:17]([NH:20][CH3:21])[CH2:18][CH3:19])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1.ClCCCl.[O-2].[Mn+4].[O-2]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:17]([NH:20][CH3:21])[CH2:18][CH3:19])=[C:6]([F:16])[C:7]=1[C:8]([C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:9]
Reactant: CC[C@@H](NC)c1ccc(Cl)c(C(O)c2cccnc2)c1F
Agent: [Mn+4]
Agent: [O-2]
Solvent: Cc1ccccc1
Solvent: ClCCCl
Product: CC[C@@H](NC)c1ccc(Cl)c(C(=O)c2cccnc2)c1F
Temperature: 100 °C

Procedure:
Step 3 A stirred suspension of {6-chloro-2-fluoro-3-[(1R)-1-(methylamino)propyl]-phenyl}(pyridin-3-yl)methanol (0.123 g, 0.398 mmol) and manganese(IV) oxide (0.693 g, 7.97 mmol) in toluene (1.99 mL) and 1,2-dichloroethane (1.99 mL) was heated at 100° C. for 2.5 hours. Upon cooling, the mixture was filtered; the residual solids were washed with DCM (×2) and concentrated. Preparative HPLC gave [(1R)-1-{4-chloro-2-fluoro-3-[(pyridin-3-yl)carbonyl]phenyl}propyl](methyl)amine which was converted to the HCl salt, 0.012 g, 9%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]2[C:21]([CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[C:22]([CH:30]=[CH:31][CH:32]=2)[O:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH:5]=[C:6]([C:8](=[O:12])[N:9]([CH3:11])[CH3:10])[CH:7]=1.O.[C:39]1(B(O)O)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(=O)([O-])[O-].[K+].[K+]>CCO.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>[C:35]([CH2:34][CH2:33][C:21]1[C:20]([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:14]#[C:13][C:4]2[CH:3]=[C:2]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:7]=[C:6]([C:8](=[O:12])[N:9]([CH3:11])[CH3:10])[CH:5]=2)=[CH:32][CH:31]=[CH:30][C:22]=1[O:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])([OH:37])=[O:36]
Reactant: CN(C)C(=O)c1cc(Br)cc(C#CCCCCCc2cccc(OCCCC(=O)O)c2CCC(=O)O)c1
Reactant: OB(O)c1ccccc1
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: [K+]
Solvent: O
Solvent: CCO
Product: CN(C)C(=O)c1cc(C#CCCCCCc2cccc(OCCCC(=O)O)c2CCC(=O)O)cc(-c2ccccc2)c1
Temperature: 78 °C

Procedure:
To a solution of 4-[3-[7-(3-bromo-5-dimethylcarbamoyl-phenyl)-hept-6-ynyl]-2-(2-carboxy-ethyl)-phenoxy]-butyric acid (100 mg, 0.17 mmol) in EtOH (4 mL)/H2O (1 mL) were added phenylboronic acid (50 mg, 0.35 mmol), potassium carbonate (100 mg, 0.7 mmol) and Pd(PPh3)4 (5 mg, 0.004 mmol). The mixture was heated at 78° C. for 5 h and then cooled to room temperature. The reaction mixture was filtered using a syringe filter 0.45 μm and the filtrate was concentrated under reduced pressure. The crude oil was then purified by preparative HPLC using acetonitrile/water gradient.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6](Cl)=[O:7].[Cl:14][C:15]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][C:16]=1[O:17][C:18]1[CH:19]=[CH:20][C:21]([N+:30]([O-:32])=[O:31])=[C:22]([CH:29]=1)[C:23]([O:25][CH2:26][CH2:27][OH:28])=[O:24].N1C=CC=CC=1>C(Cl)Cl>[Cl:14][C:15]1[CH:36]=[C:35]([C:37]([F:39])([F:38])[F:40])[CH:34]=[CH:33][C:16]=1[O:17][C:18]1[CH:19]=[CH:20][C:21]([N+:30]([O-:32])=[O:31])=[C:22]([CH:29]=1)[C:23]([O:25][CH2:26][CH2:27][O:28][C:6](=[O:7])[CH2:5][O:4][C:3]1[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:2]=1[Cl:1])=[O:24]
Reactant: O=C(Cl)COc1ccc(Cl)cc1Cl
Reactant: O=C(OCCO)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(COc1ccc(Cl)cc1Cl)OCCOC(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 60 °C
Yield: 1.5 %

Procedure:
2,4-Dichlorophenoxyacetyl chloride (5.3 g, 0.25 mole), was added portionwise to a solution of 2-hydroxyethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (10 g, 0.25 mole) and pyridine (70 ml). The resulting mixture was heated to 60° C. for 1 hr., cooled and taken into 500 ml CH2Cl2. The methylene chloride solution was washed two times with water, dried and concentrated to 12.5 g of gummy material. The crude gum was chromatographed through silica gel (3:10, ethyl acetate:hexane) to give 2.3 g of pure 2-(2,4-dichlorophenoxyacetoxy)ethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate; nmr (DMSO) 4.20-4.76 (m, 4H), 5.04 (S, 2H), 6.96-8.42 (m, 9H); ir (CHCl3) 1755, 1770 Cm-1.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[C:18]([F:19])[C:13]=3[N:12]([C:20]([CH3:31])([CH3:30])[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[F:32][C:33]([F:45])([F:44])[C:34]1[CH:35]=[C:36]([CH2:40][C:41](O)=[O:42])[CH:37]=[CH:38][CH:39]=1.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[C:26]([Si:23]([CH3:24])([CH3:25])[O:22][CH2:21][C:20]([N:12]1[C:13]2[C:18]([F:19])=[CH:17][N:16]=[CH:15][C:14]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH2:40][C:36]3[CH:37]=[CH:38][CH:39]=[C:34]([C:33]([F:44])([F:32])[F:45])[CH:35]=3)[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1)([CH3:31])[CH3:30])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N)c2)c2cncc(F)c21
Reactant: O=C(O)Cc1cccc(C(F)(F)F)c1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(NC(=O)Cc3cccc(C(F)(F)F)c3)c2)c2cncc(F)c21
Temperature: 25 °C
Reaction time: 18 h
Yield: 86.6 %

Procedure:
To a solution of (5-amino-pyridin-3-yl)-{1-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridin-3-yl}-methanone (Preparation 29, 35 mg, 79 μmol), (3-trifluoromethyl-phenyl)-acetic acid (21.8 mg, 106 μmol) and DIPEA (48.94 μL, 277 μmol) in THF (3 mL), T3P (160 μL, 277 μmol) was added and the mixture stirred at 25° C. for 18 hours. The reaction was evaporated under reduced pressure, the residue partitioned between water and ethyl acetate, the organic extracts washed with saturated sodium bicarbonate solution, dried over sodium sulphate, evaporated in vacuo and triturated with pentane-ether to afford the title compound as a white solid (87%, 43 mg).
Reaction SMILES: [CH3:1][Si:2]([CH3:11])([CH:9]=[CH2:10])[O:3][Si:4]([CH3:8])([CH3:7])[CH:5]=[CH2:6].[CH:12]#[C:13][CH2:14][CH2:15][CH2:16]CC>C1(C)C=CC=CC=1>[C:5]([Si:4]([CH3:8])([CH3:7])[O:3][Si:2]([CH3:1])([CH3:11])[CH:9]=[CH2:10])#[C:6][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: C=C[Si](C)(C)O[Si](C)(C)C=C
Reactant: C#CCCCCC
Solvent: Cc1ccccc1
Product: C=C[Si](C)(C)O[Si](C)(C)C#CCCCCC

Procedure:
As in reaction conditions of Example XIX Step 1, to 6.25 mL of toluene, the 0.05 g carbonylchlorohydridebis(triisopropylphosphine)ruthenium(II) was added, and the reaction was carried out between 2.87 g 1,1,3,3-tetramethyl-1,3-divinyldisiloxane and 0.49 g 1-heptyne. Raw 1-(1-heptynyl)-1,1,3,3-tetramethyl-3-vinyldisiloxane was obtained.
Reaction SMILES: Cl.[CH2:2]1[C:6]2([CH2:11][CH2:10][N:9]([NH2:12])[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[C:30]3[N:31]([C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=4[Cl:44])[N:32]=[C:33]([C:34](Cl)=[O:35])[C:29]=3[S:28][CH2:27][C:25]=2[CH:26]=1>C(Cl)Cl>[CH2:2]1[C:6]2([CH2:11][CH2:10][N:9]([NH:12][C:34]([C:33]3[C:29]4[S:28][CH2:27][C:25]5[CH:26]=[C:21]([Cl:20])[CH:22]=[CH:23][C:24]=5[C:30]=4[N:31]([C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][C:38]=4[Cl:44])[N:32]=3)=[O:35])[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3]1
Reactant: NN1CCC2(CCCC2)CC1
Reactant: O=C(Cl)c1nn(-c2ccc(Cl)cc2Cl)c2c1SCc1cc(Cl)ccc1-2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NN1CCC2(CCCC2)CC1)c1nn(-c2ccc(Cl)cc2Cl)c2c1SCc1cc(Cl)ccc1-2
Temperature: 25 °C
Reaction time: 4 h
Yield: 58.9 %

Procedure:
A solution of 0.28 g of 8-azaspiro[4.5]dec-8-ylamine hydrochloride and 0.41 ml of triethylamine in 15 ml of DCM is cooled to 0° C., 0.6 g of the acid chloride prepared in Example 1, step A, in 10 ml of DCM is added dropwise and the mixture is left for 4 hours, with stirring, at RT. The mixture is extracted with DCM, the organic phase is washed with water, with a saturated NaCl solution, dried over Na2SO4 and the solvent is evaporated under vacuum. The residue is chromatographed on silica gel, eluting with the toluene/AcOEt (95/5; v/v) mixture. 0.45 g of the expected compound is obtained in amorphous form.
Reaction SMILES: [C:1]([C:5]1[CH:42]=[CH:41][C:8]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2/[CH:17]=[CH:18]/[CH:19]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[CH:35][CH:34]=2)[CH2:20][CH2:21][C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C[Si]([N:47]=[N+:48]=[N-:49])(C)C.C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:42]=[CH:41][C:8]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2/[CH:17]=[CH:18]/[CH:19]([CH2:32][C:33]2[CH:34]=[CH:35][C:36]([C:39]3[NH:49][N:48]=[N:47][N:40]=3)=[CH:37][CH:38]=2)[CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:30][CH:31]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc(CCC(/C=C/c2ccccc2OCc2ccc(C(C)(C)C)cc2)Cc2ccc(C#N)cc2)cc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc(CCC(/C=C/c2ccccc2OCc2ccc(C(C)(C)C)cc2)Cc2ccc(-c3nnn[nH]3)cc2)cc1
Temperature: 80 °C

Procedure:
A solution of 180 mg (0.32 mmol) of methyl 4-[(4E)-5-{2-[(4-tert-butylbenzyl)oxy]phenyl}-3-(4-cyanobenzyl)pent-4-en-1-yl]benzoate in 10 ml of toluene is mixed with 557.3 mg (4.84 mmol) of trimethylsilyl azide and 120.51 mg (0.48 mmol) of di-n-butyltin oxide and heated at 80° C. for 12 hours. After cooling to room temperature, the mixture is washed with saturated sodium bicarbonate solution. The organic phase is separated off, washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration the filtrate is concentrated to dryness. The resulting crude product is purified on a silica gel column (mobile phase: cyclohexan/ethyl acetate 2:1→1:2). 88 mg (0.14 mmol, 43% of theory) of a white foam are obtained.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:15][CH2:14][CH2:13][C:7]=3[C:8](=[O:12])[NH:9][C:10]=2[CH:11]=1.C([Sn](CCCC)(CCCC)[C:21]1[O:22][CH:23]=[CH:24][CH:25]=1)CCC>C1(C)C=CC=CC=1.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:22]1[CH:23]=[CH:24][CH:25]=[C:21]1[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:15][CH2:14][CH2:13][C:7]=3[C:8](=[O:12])[NH:9][C:10]=2[CH:11]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccco1
Reactant: O=c1[nH]c2cc(Br)ccc2c2c1CCC2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: O=c1[nH]c2cc(-c3ccco3)ccc2c2c1CCC2
Temperature: 25 °C
Reaction time: 15 h
Yield: 105.9 %

Procedure:
A suspension of 1.32 g (5.0 mmol) of 7-bromo-1,2,3,5-tetrahydrocyclo-penta[c]quinolin-4-one in 200 mL of toluene is mixed with 1.7 ml (5.5 mmol) of 2-(tributyl-stannyl)furan and 0.29 g (0.25 mmol) of tetrakis(triphenylphosphine)palladium. The reaction mixture is degassed, aerated with nitrogen, stirred for 15 hours at room temperature and heated for 4.5 hours to 110° C. The batch is mixed with silica gel and concentrated by evaporation in a vacuum. Column chromatography of the residue on silica gel with hexane-ethyl acetate yields 1.33 g of product.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([B:10]2[O:14][C:13]([CH3:16])([CH3:15])[C:12]([CH3:18])([CH3:17])[O:11]2)[CH:7]=[CH:6][C:4]=1[NH2:5].[CH3:19][N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21]1[C:29](Cl)=[O:30]>CN(C)C1C=CN=CC=1.ClCCl.N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:9]=[C:8]([B:10]2[O:14][C:13]([CH3:16])([CH3:15])[C:12]([CH3:18])([CH3:17])[O:11]2)[CH:7]=[CH:6][C:4]=1[NH:5][C:29]([C:21]1[N:20]([CH3:19])[C:28]2[C:23]([CH:22]=1)=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:30]
Reactant: Cn1c(C(=O)Cl)cc2ccccc21
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1N
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1NC(=O)c1cc2ccccc2n1C
Temperature: 25 °C
Reaction time: 96 h
Yield: 92.1 %

Procedure:
To a solution of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (4.01 mmol, 1 g) and 4-dimethylaminopyridine (0.401 mmol, 0.049 g) in dichloromethane (5 ml) and pyridine (5 ml) was added 1-methyl-1H-indole-2-carbonyl chloride (5.22 mmol, 1.010 g) and this solution was stirred at room temperature for four days. The reaction mixture was concentrated and coevaporated with toluene. To the residue dichloromethane and water were added. The organic layer was separated, dried (sodium sulfate) and concentrated in vacuo. Purification using flash chromatography (silica gel, dichloromethane) yielded N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide (1.5 g).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].[Cl-].[NH4+]>CN(C=O)C.CCOCC>[Si:21]([O:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(C)(C)OC(=O)N1CCOC(CO)C1
Agent: [Cl-]
Agent: [NH4+]
Agent: c1c[nH]cn1
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCOC(CO[Si](C)(C)C(C)(C)C)C1
Temperature: 25 °C
Reaction time: 48 h
Yield: 99.5 %

Procedure:
To a round bottom flask charged with (+/−)-tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (2 g, 9.21 mmol) in DMF (2 mL) was added imidazole and TBS-Cl (1.387 g, 9.21 mmol). The reaction mixture was stirred at room temperature 2 d. The reaction mixture was poured into a separatory funnel containing half-saturated aqueous ammonium chloride and ether. The aqueous layer was extracted with ether (2×). The combined organics were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. (+/−)-tert-Butyl 2-(((tert-butyldimethylsilyl)oxy)methyl)morpholine-4-carboxylate (3.039 g) was isolated as a white pasty solid.
Reaction SMILES: [Br:1]B1C2CCCC1CCC2.C(Cl)Cl.[C:14]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)#[CH:15].C(O)(=O)C.[OH-].[Na+].OO>>[Br:1][C:14]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)=[CH2:15]
Reactant: BrB1C2CCCC1CCC2
Reactant: C#CC1CCCCC1
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CC(=O)O
Product: C=C(Br)C1CCCCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 9-bromo-9-bora-bicyclo[3.3.1]nonane 1 M in DCM (33 mL, 33 mmol) at 0° C. was added ethynylcyclohexane (3.6 mL, 28 mmol) under argon via syringe slowly dropwise in portions over 10 min. The reaction mixture was allowed to stir 3 h, at which point acetic acid (4.8 mL, 83 mmol) was added dropwise in portions over 20 min. After 1 h additional, sodium hydroxide (17 mL, 166 mmol) was added slowly, followed by cautious addition of hydrogen peroxide (8.5 mL, 83 mmol). The reaction mixture was allowed to stir rapidly 1 h, then was warmed to ambient temperature. The reaction mixture was partitioned between hexanes and water, and the organic layer was washed with saturated aq. Sodium bicarbonate, and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting liquid was filtered through a 3 cm pad of silica gel, rinsing with 200 mL hexanes, and the filtrate was concentrated in vacuo to give crude (1-bromovinyl)-cyclohexane as a clear/colorless oil which was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[C:3]([I:16])=[C:4]([C:13]([Cl:15])=[O:14])[C:5]([I:12])=[C:6]([C:10]=1[I:11])[C:7]([Cl:9])=[O:8].[CH3:17][O:18][CH2:19][C:20](Cl)=[O:21].O>CC(N(C)C)=O>[CH3:17][O:18][CH2:19][C:20]([NH:1][C:2]1[C:10]([I:11])=[C:6]([C:7]([Cl:9])=[O:8])[C:5]([I:12])=[C:4]([C:3]=1[I:16])[C:13]([Cl:15])=[O:14])=[O:21]
Reactant: COCC(=O)Cl
Reactant: Nc1c(I)c(C(=O)Cl)c(I)c(C(=O)Cl)c1I
Solvent: CC(=O)N(C)C
Solvent: O
Product: COCC(=O)Nc1c(I)c(C(=O)Cl)c(I)c(C(=O)Cl)c1I
Temperature: 5 °C

Procedure:
5-Amino-2,4,6-triiodoisophthaloyl chloride prepared in Example 1 (59.6 g, 0.1 g-mole) is dissolved in DMAc (100 ml). The solution is cooled to 5° C. and methoxyacetyl chloride (21.7 g 0.2 g-mole) is added slowly keeping the temperature at 5°-10° C. When the addition is complete, the reaction mixture is allowed to warm to room temperature and stirred until the reaction is complete. The solution is cooled to room temperature and poured slowly into 1 L of cold water (0°-5° C.) with stirring to precipitate the product.