Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1.[CH:9]1([CH2:15][N:16]2[CH2:24][C:23]3[C:18](=[C:19]([CH3:32])[CH:20]=[C:21]([CH2:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:22]=3)[C:17]2=[O:33])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(#N)C>O>[CH:9]1([CH2:15][N:16]2[CH2:24][C:23]3[C:18](=[C:19]([CH3:32])[CH:20]=[C:21]([CH2:25][CH:26]4[CH2:27][CH2:28][N:29]([CH2:2][C:3]5[N:8]=[CH:7][CH:6]=[CH:5][N:4]=5)[CH2:30][CH2:31]4)[CH:22]=3)[C:17]2=[O:33])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: ClCc1ncccn1
Reactant: Cc1cc(CC2CCNCC2)cc2c1C(=O)N(CC1CCCCC1)C2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: Cc1cc(CC2CCN(Cc3ncccn3)CC2)cc2c1C(=O)N(CC1CCCCC1)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.7 %

Procedure:
To a mixture of 2-Chloromethylpyrimidine (32 mg, 0.247 mmol), 2-Cyclohexylmethyl-7-methyl-5-piperidin-4-ylmethyl-2,3-dihydro-isoindol-1-one (56 mg, 0.164 mmol) and cesium carbonate (160 mg, 0.492 mmol) was added acetonitrile (3.0 mL). The mixture was allowed to stir at room temperature overnight. Water (2.0 mL) was added and the product was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate, filtered and concentrated. Column chromatography provided the title compound as a yellow oil (48 mg, 69%). 1H NMR (300 Adz, CDCl3): δ 8.76-8.72 (d, 2H), 7.18 (t, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 4.30 (s, 2H), 3.78 (s, 2H), 3.40-3.37 (d, 2H), 2.97-2.93 (d, 2H), 2.70 (s, 3H), 2.58-2.56 (d, 2H), 2.10-2.05 (t, 2H), 1.71-1.42 (m, 10H), 1.26-1.13 (m, 4H), 1.09-0.98 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:40]=[C:41]([F:43])[CH:42]=1)[CH2:5][C@@H:6]([C@@H:10]([CH:12]1[CH2:21][C:20]2[C:15](=[C:16]([O:22][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH:17]=[CH:18][CH:19]=2)[CH2:14][N:13]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[OH:11])C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:51])C=CC=CC=1.C([N:63]([CH2:66]C)CC)C>C1(C)C=CC=CC=1>[F:43][C:41]1[CH:40]=[C:4]([CH:3]=[C:2]([F:1])[CH:42]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:12]2[CH2:21][C:20]3[C:15](=[C:16]([O:22][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:24]([CH3:25])[CH3:26])[CH:27]([CH3:29])[CH3:28])[CH:17]=[CH:18][CH:19]=3)[CH2:14][N:13]2[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[O:11][C:66](=[O:51])[NH:63]1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CC(C)[Si](Oc1cccc2c1CN(C(=O)OC(C)(C)C)C([C@@H](O)[C@H](Cc1cc(F)cc(F)c1)C(=O)O)C2)(C(C)C)C(C)C
Reactant: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(C)[Si](Oc1cccc2c1CN(C(=O)OC(C)(C)C)[C@@H]([C@H]1OC(=O)N[C@H]1Cc1cc(F)cc(F)c1)C2)(C(C)C)C(C)C
Reaction time: 3 h
Yield: 29.6 %

Procedure:
To a solution of (2S,3S)-2-(3,5-difluorobenzyl)-3-(2-(tert-butoxycarbonyl)-8-(triisopropylsilyloxy)-1,2,3,4-tetrahydroisoquinolin-3-yl)-3-hydroxypropanoic acid (Step F (10), 2.0 g, 2.57 mmol) in toluene (150 mL) was added diphenylphosphoryl azide (1.13 g, 4.12 mmol) and triethyl amine (649 mg, 6.43 mmol.). This reaction mixture was brought to 50° C. for 2 h and 100° C. for 3 h. The mixture was concentrated under vacuum and purified by silica gel Flash Chromatography to give 470 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.12 (18H, m), 1.28-1.36 (3H, m), 1.48 (9H, s), 2.71 (1H, m), 3.08 (2H, s), 3.18-3.22 (1H, m), 3.82 (1H, m), 4.59 (1H, m), 4.76-5.04 (2H, m), 5.11 (1H, s), 6.67-6.77 (5H, m), 7.06 (1H, m).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:14](=[O:16])[CH3:15])[CH:8]=[C:9]([OH:13])[C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].Br[CH2:18][CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1>>[C:1]([C:5]1[CH:6]=[C:7]([C:14](=[O:16])[CH3:15])[CH:8]=[C:9]([O:13][CH2:18][CH2:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[C:10]=1[O:11][CH3:12])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1c(O)cc(C(C)=O)cc1C(C)(C)C
Reactant: BrCCOC1CCCCO1
Product: COc1c(OCCOC2CCCCO2)cc(C(C)=O)cc1C(C)(C)C
Yield: 84.7 %

Procedure:
Analogously to O2.071, 1-(3-tert-butyl-5-hydroxy-4-methoxyphenyl)ethanone (O3.070; 5.0 g) was reacted with 2-(2-bromoethoxy)tetrahydropyran (5.64 g). However, the crude product was purified using silica gel (40 g cartridge, n-heptane/EA gradient of 0-50% within 60 min). 6.68 g of the title compound were obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[N:10][C:11](=O)[NH:12][N:13]=1.C(Cl)(Cl)[Cl:16].P(Cl)(Cl)(Cl)=O>CN(C)C=O>[Cl:16][C:11]1[N:12]=[N:13][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[CH:9][N:10]=1
Reactant: ClC(Cl)Cl
Reactant: O=c1ncc(-c2ccccc2Cl)n[nH]1
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Product: Clc1ncc(-c2ccccc2Cl)nn1

Procedure:
A suspension of 53 g. of 6-(o-chlorophenyl)-1,2,4-triazin-3(2H)-one in 400 ml. of chloroform is cooled in an ice bath and 400 ml. of phosphorus oxychloride is added followed by 3 g. of N,N-dimethylformamide. The mixture is refluxed overnight and treated as described in Example 12, giving 3-chloro-6-(o-chlorophenyl)-1,2,4-triazine as white needles.
Reaction SMILES: [C:1]1([C:7]2[N:12]3[N:13]=[N:14][N:15]=[C:11]3[N:10]3[N:16]=[CH:17][N:18]=[C:9]3[C:8]=2[CH2:19][CH2:20][OH:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]12([C:32](Cl)=[O:33])[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2>N1C=CC=CC=1.C(Cl)Cl>[C:22]12([C:32]([O:21][CH2:20][CH2:19][C:8]3[C:9]4[N:10]([N:16]=[CH:17][N:18]=4)[C:11]4[N:12]([N:13]=[N:14][N:15]=4)[C:7]=3[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[O:33])[CH2:29][CH:28]3[CH2:27][CH:26]([CH2:25][CH:24]([CH2:30]3)[CH2:23]1)[CH2:31]2
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Reactant: OCCc1c(-c2ccccc2)n2nnnc2n2ncnc12
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(OCCc1c(-c2ccccc2)n2nnnc2n2ncnc12)C12CC3CC(CC(C3)C1)C2
Reaction time: 1 h

Procedure:
To a solution containing 1.4 g of 5-phenyltetrazolo[1,5-a][1,2,4]triazolo[1,5-c]pyrimidine-6-ethanol (0.005 mole) dissolved in 12 ml of pyridine is added 1.0 g of 1-adamantanecarbonyl chloride (0.005 mole). The reaction mixture is stirred for one hour and then allowed to stand overnight at room temperature. The reaction mixture is evaporated to dryness yielding a residue. The residue is taken up in methylene chloride, extracted with water, dried over sodium sulfate and evaporated to dryness yielding a crude product. The crude product is chromatographed on silica gel to yield 2-(5-phenyltetrazolo[1,5-a][1,2,4]triazolo[1,5-c]pyrimidin-6-yl)ethyl tricyclo[3.3.1.13,7 ]decane-1-carboxylate having the structural formula ##STR25## and the azido tautomer thereof as a white solid having a melting point of 129°-130° C. and the following elemental analysis:
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][C:10](=[O:12])[NH:9][C:8]2[N:7]=[C:6]([C:13]#[N:14])[C:5]3[N:15]=[CH:16][CH:17]=[CH:18][C:4]=3[C:3]1=2.S(=O)(=O)(O)[OH:20].C([O-])([O-])=O.[Na+].[Na+]>>[CH3:1][CH:2]1[CH2:11][C:10](=[O:12])[NH:9][C:8]2[N:7]=[C:6]([C:13](=[O:20])[NH2:14])[C:5]3[N:15]=[CH:16][CH:17]=[CH:18][C:4]=3[C:3]1=2
Reactant: O=S(=O)(O)O
Reactant: CC1CC(=O)Nc2nc(C#N)c3ncccc3c21
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CC1CC(=O)Nc2nc(C(N)=O)c3ncccc3c21
Yield: 63 %

Procedure:
2 g (0.008 mol) of 1-methyl-6-cyano-1,2-dihydropyrido[2,3-c][1,8]naphthyridin-3(4H)-one are allowed to stand for 3 hours at room temperature in 40 ml of 96% strength sulphuric acid. After neutralization using aqueous Na2CO3 solution, the mixture is extracted repeatedly with methylene chloride, the combined organic bases are dried and then evaporated in vacuo, and the residue is chromatographed on silica gel with chloroform/methanol 98:2. 1.29 g (63% of theory) of 1-methyl-6- carbamoyl-dihydropyrido[2,3-c][1,8]naphthyridin-3(4H)-one are obtained.
Reaction SMILES: [C:1]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH:6]=1)([O:3][CH3:4])=[O:2].[N+:15]([C:18]1[CH:19]=[C:20]([CH2:24][CH2:25][N+:26]([O-:28])=[O:27])[CH:21]=[CH:22][CH:23]=1)([O-:17])=[O:16].N12CCCN=C1CCCCC2>C(#N)C.C(OCC)(=O)C>[C:1]([CH:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH:6]1[CH:25]([N+:26]([O-:28])=[O:27])[CH2:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([N+:15]([O-:17])=[O:16])[CH:19]=1)([O:3][CH3:4])=[O:2]
Reactant: COC(=O)C1=CCCc2ccccc21
Reactant: O=[N+]([O-])CCc1cccc([N+](=O)[O-])c1
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)C1c2ccccc2CCC1C(Cc1cccc([N+](=O)[O-])c1)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.2 %

Procedure:
To a mixture of 2 g (10.6 mmol) of 1-carbomethoxy-3,4-dihydronaphthalene, from Step 1 of Example 46, and 2.08 g (10.6 mmol) of 2-(3-nitrophenyl)-1-nitroethane, from Step 2, in 1 mL of acetonitrile was added 0.2 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reaction mixture was stirred at ambient temperature for 0.5 h and then diluted with ethyl acetate. The reaction mixture was washed with 2N aqueous hydrochloric acid solution. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give 3.96 g (97% yield) of the title compound as a mixture of diastereomers which was taken on without purification to the next step; MS DCI-NH3M/Z: 402 (M+NH4)+ ; 1H NMR (CDCl3) δ1.52-1.86 (1H, m), 2.1-2.35 (1H, m), 2.42-2.65 (1H, m), 2.78- 3.15 (2H, m), 3.2-3.33 (1H, m), 3.38-3.55 (1H, m). 3.78-3.81 (3H, s), 3.91-4.18 (1H, m), 4.68-4.88 (1H, m), 7.12-7.42 (4H, m), 7.48-7.58 (2H, m), 8.01-8.18 (2H, m).
Reaction SMILES: C([Li])CCC.C(N[CH:10]([CH3:12])[CH3:11])(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[O:24][C:23]([CH3:26])([CH3:25])[O:22][C:21]2=[O:27])=[CH:16][CH:15]=1.C(Br)C#C>O1CCCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2([CH2:12][C:10]#[CH:11])[O:24][C:23]([CH3:25])([CH3:26])[O:22][C:21]2=[O:27])=[CH:18][CH:19]=1
Reactant: CC(C)NC(C)C
Reactant: CC1(C)OC(=O)C(c2ccc(Cl)cc2)O1
Agent: C#CCBr
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C#CCC1(c2ccc(Cl)cc2)OC(C)(C)OC1=O
Reaction time: 1.5 h

Procedure:
3.3 ml of butyl lithium (1.6 molar in hexane) are added under stirring to a solution of 0.8 ml diisopropylamine in 20 ml tetrahydrofurane at −78° C. under nitrogen. After stirring for 30 minutes at the same temperature, 1.13 g of 5-(4-chloro-phenyl )-2,2-dimethyl-(1,3)-dioxolan-4-one in 5 ml tetrahydrofurane are added and stirring is continued for 1.5 hours. Then the reaction mixture is treated with a solution of 0.57 ml propargyl bromide in 3 ml tetrahydrofurane. Stirring is continued at about 60° C. over the night. Then the reaction is quenched with HCl 1N (pH 6) and ice and water and extracted with diethyl ether. The extracts are dried over sodium sulfate and evaporated. The 5-(4-chloro-phenyl)-2,2-dimethyl-5-prop-2-ynyl-(1,3)dioxolan-4-one remains as a oil which is used directly for the next step.
Reaction SMILES: [O:1]=[S:2]1(=[O:18])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][C:8]=1[O:16][CH3:17].Cl.[NH:20]1[CH2:25][CH2:24][CH:23]([C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=[O:27])[CH2:22][CH2:21]1.CN1CCOCC1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO.O>[O:18]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([N:20]2[CH2:25][CH2:24][CH:23]([C:26](=[O:27])[C:28]3[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=3)[CH2:22][CH2:21]2)=[O:13])=[CH:9][C:8]=1[O:16][CH3:17]
Reactant: COc1cc(C(=O)O)ccc1N1CCCS1(=O)=O
Reactant: Cc1ccc(C(=O)C2CCNCC2)cc1
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: Cl
Agent: [Cl-]
Solvent: CN1CCOCC1
Solvent: O
Solvent: CO
Product: COc1cc(C(=O)N2CCC(C(=O)c3ccc(C)cc3)CC2)ccc1N1CCCS1(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.7 %

Procedure:
A mixture of 4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-3-methoxybenzoic acid (285 mg) described in Preparation Example 21, (piperidin-4-yl) (p-tolyl)methanone hydrochloride (252 mg) and N-methylmorpholine (0.12 mL) was dissolved in a solution of methanol (3 mL) and water (2 mL), 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (349 mg) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform:methanol) to give the title compound (344 mg).
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=4)[N:13]([CH2:22][CH3:23])[CH:12]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH:24](Br)(C)C>>[O:4]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=4)[N:13]([CH:22]([CH3:24])[CH3:23])[CH:12]=3)[CH2:7][CH2:6]2)[O:1][CH2:2][CH2:3]1
Reactant: CC(C)Br
Reactant: CCn1cc(C2CCC3(CC2)OCCO3)c2cc(C#N)ccc21
Product: CC(C)n1cc(C2CCC3(CC2)OCCO3)c2cc(C#N)ccc21
Yield: 62 %

Procedure:
This compound was prepared in the manner described above for intermediate 5b by replacing ethylbromide with isopropylbromide (10.2 g, 83 mmol) in 62% yield (6.44 g) as a white solid: mp 114.5-116° C.; MS EI m/e 324 (M+)
Reaction SMILES: [F:1][CH:2]([F:24])[O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[C:12]([C:17](=O)/[CH:18]=[CH:19]/[N:20](C)C)=[N:11]2)[CH:7]=[CH:8][CH:9]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[NH:33]N>>[F:1][CH:2]([F:24])[O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[C:12]([C:17]3[N:33]([C:27]4[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=4[F:25])[N:20]=[CH:19][CH:18]=3)=[N:11]2)[CH:7]=[CH:8][CH:9]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(OC(F)F)c2)ccc1=O
Reactant: NNc1cc(F)ccc1F
Product: O=c1ccn(-c2cccc(OC(F)F)c2)nc1-c1ccnn1-c1cc(F)ccc1F

Procedure:
The product was obtained starting from 1-(3-Difluoromethoxy-phenyl)-3-((E)-3-dimethylamino-acryloyl)-1H-pyridazin-4-one (A-10) and 2,5-difluoro-phenylhydrazine according to the method described for example 91. MS: M=417.2 (M+H)+
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].B(F)(F)F.CCOCC.[CH3:19][C:20]1([CH:26]=[CH2:27])[O:25][C:23](=[O:24])[CH2:22][CH2:21]1>O1CCOCC1.CCOCC>[CH3:19][C:20]1([CH2:21][CH2:22][C:23]([OH:25])=[O:24])[CH2:26][CH2:27][C:4]2[C:3](=[C:2]([CH3:1])[C:7]([CH3:8])=[CH:6][CH:5]=2)[O:9]1
Reactant: Cc1cccc(O)c1C
Reactant: C=CC1(C)CCC(=O)O1
Agent: FB(F)F
Solvent: CCOCC
Solvent: C1COCCO1
Product: Cc1ccc2c(c1C)OC(C)(CCC(=O)O)CC2
Temperature: 25 °C

Procedure:
To a solution of 2,3-dimethylphenol (0.01 mol) and boron trifluoride diethyl etherate (0.016 mol) in dioxane (10 mL, dried on sodium) in a flask was added γ-methyl-γ-vinylbutyrolactone (0.016 mol) in dioxane (5.0 mL) via syringe pump over 50 min at 110° C. (oil bath, reflux) under nitrogen. The reaction mixture was cooled to room temperature and diluted with ether (200 mL), then washed with water (100 mL, 2×50 mL) and dried over sodium sulfate. Ether was then removed in vacuum. The residue was dissolved in methanol (30 mL), and solvent was removed in vacuum. The reaction mixture was purified by flash column chromatography on silica gel (eluent ethyl acetate/hexane, 1:1). Fractions containing the desired chroman were pooled, solvent was removed, and the compound was crystallized from ethyl acetate/hexane. M.P.: 93-94° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[C:12]([CH3:25])=[N:13][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=4)[C:15]=3[CH3:16])=[CH:9][N:8]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:5]2=[N:6][CH:7]=1.[CH3:36][N:37]([CH3:61])[CH2:38][CH2:39][O:40][C:41]1[CH:46]=[CH:45][C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][C:42]=1NS(C)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O>[F:24][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[CH2:17][N:14]1[C:15]([CH3:16])=[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:44]4[CH:45]=[CH:46][C:41]([O:40][CH2:39][CH2:38][N:37]([CH3:61])[CH3:36])=[CH:42][CH:43]=4)[CH:3]=3)[N:8]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=3)(=[O:28])=[O:27])[CH:9]=2)[C:12]([CH3:25])=[N:13]1
Reactant: CN(C)CCOc1ccc(B2OC(C)(C)C(C)(C)O2)cc1NS(C)(=O)=O
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3c(C)nn(Cc4cccc(F)c4)c3C)c3cc(Br)cnc32)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3c(C)nn(Cc4cccc(F)c4)c3C)c3cc(-c4ccc(OCCN(C)C)cc4)cnc32)cc1
Yield: 45.3 %

Procedure:
Using similar reaction conditions as described in step-ii of example-1, 5-bromo-3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (compound of step 1 of Example 14) (100 mg, 0.18 mmol) was coupled with N-(2-(2-(dimethylamino)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methane sulfonamide (Intermediate 27) (229 mg, 0.596 mmol) in sodium carbonate (57 mg, 0.54 mmol) Pd(PPh3)2Cl2 (6 mg, 0.009 mmol), Toluene/ethanol/water (5/2.5/1 ml) to afford 52 mg (39.39% yield) of the titled compound after purification by preparative TLC (SiO2-eluted by 5% methanolic ammonia in DCM). MS: m/z=731.4 (M+1).
Reaction SMILES: [C:1]1([PH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C[O:17]CC1.[Li]CCCC.Cl[CH2:25]/[CH:26]=[C:27]1\[C:28](=[CH2:69])[C@@H:29]([O:51][Si:52]([C:65]([CH3:68])([CH3:67])[CH3:66])([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH2:30][C@@H:31]([O:33][Si:34]([C:47]([CH3:50])([CH3:49])[CH3:48])([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:32]\1>O>[C:65]([Si:52]([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)[O:51][C@H:29]1[CH2:30][C@@H:31]([O:33][Si:34]([C:47]([CH3:48])([CH3:49])[CH3:50])([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:32]/[C:27](=[CH:26]/[CH2:25][P:7](=[O:17])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)/[C:28]1=[CH2:69])([CH3:66])([CH3:67])[CH3:68]
Reactant: C=C1/C(=C\CCl)C[C@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C[C@@H]1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: C1CCOC1
Reactant: c1ccc(Pc2ccccc2)cc1
Agent: [Li]CCCC
Solvent: O
Product: C=C1/C(=C\CP(=O)(c2ccccc2)c2ccccc2)C[C@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C[C@@H]1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reaction time: 1.25 h

Procedure:
847 μl (10.2 mmol) of diphenylphosphine in 16 ml of abs. THF was deprotonated at -10° with 3.05 ml nBuLi (1.5 M, hexane). The solution was then cooled to -75° and 2.76 g (4.15 mmol) of (Z)-(3S,5S)-1-(2-chloroethylidene)-3,5-bis-(tert-butyl-diphenyl-silanyloxy)-2-methylenecyclohexane, dissolved in 16 ml of abs. THF, was added dropwise. 10 Minutes later, 190 μl of water was injected and the reaction mixture allowed to reach room temperature. All solvents were then removed i.V., the residue taken up in 33 ml of CH2Cl2 and treated with 81 ml of 5% H2O2. After stirring for 75 minutes, the layers were separated, the aqueous phase extracted with AcOEt, the organic layers washed with sodium pyrosulfite, dried over sodium sulfate and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=45/55) afforded 2.534 g of (Z)-(3S,5S)-[2[-3,5-bis-(tert-butyl-diphenyl-silanyloxy)-2-methylenecyclohexylidene]-ethyl]-diphenyl-phosphine oxide as colorless foam.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][C@@H:12]2[CH2:16][O:15][C@@H:14]3[C@H:17](OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:18][O:19][C@H:13]23)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Br-:31].[Li+].O>CN(C)C=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][C@@H:12]2[CH2:16][O:15][C@@H:14]3[C@@H:17]([Br:31])[CH2:18][O:19][C@H:13]23)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: [Br-]
Reactant: Cc1ccc(S(=O)(=O)O[C@@H]2CO[C@H]3[C@@H]2OC[C@H]3OS(=O)(=O)c2ccc(C)cc2)cc1
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(S(=O)(=O)O[C@@H]2CO[C@H]3[C@@H]2OC[C@@H]3Br)cc1
Temperature: 100 °C
Yield: 21.2 %

Procedure:
A stirred mixture of ditosylate (39) (16.9 g, 37.22 mmol) and lithium bromide (4.85 g, 55.84 mmol) in N,N-dimethylformamide (100 mL) was heated at 100° C. for 27 hours. The mixture was allowed to cool then water (150 mL) added before extracting with tert-butyl methyl ether (1×100 mL then 5×50 mL). The organic phase was dried (MgSO4), filtered and reduced in vacuo to give a colourless oil which solidified on standing. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 0:100 to 80:20 gave bromotosylate (46) as a white solid (2.86 g, 29%). TLC (Rf=0.45 diethyl ether heptane, 1:1), analytical HPLC: Rf=16.768 min; HPLC-MS: 363.1/365.0 [M+H]+, 380.1/382.1, 749.0/751.0 [2M+Na]+; [□]D18+64.7° (c=8.5, CHCl3); δH (500 MHz, CDCl3) 2.45 (3H, s, CH3), 3.74 (1H, dd, 7.05 Hz, CH2), 3.95 (1H, dd, 6.47 Hz, CH2), 4.14-4.22 (2H, m, CH2), 4.29 (1H, d, J=3.03 Hz, CHBr), 4.68 (1H, d, J=4.03 Hz, CHCH), 4.76 (1H, t, J=4.48 Hz, CHOTs), 4.87 (1H, m, CHCH), 7.36 (2H, brd, J=7.97 Hz, aromatic CH3CCH), 7.83 (2H, brd, J=8.33 Hz, aromatic OSO2CCH). δC (125 MHz, CDCl3) 21.69 (CH3), 50.06 (CHBr), 70.26 (CH2CHOTs), 76.54 (CH2CHBr), 78.27 (CHOTs), 80.17 and 88.80 (CHCHCHOTs), 127.98 and 129.94 (aromatic CH), 133.01 (CHOSO2C quaternary), 145.28 (CH3C quaternary).
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C:6]1[CH:20]=[C:19]2[C:9]([NH:10][CH:11]=[C:12]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:8][CH:7]=1)=[O:4].[Br:21]N1C(=O)CCC1=O.[OH-].[Na+]>C(O)(=O)C.CO.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:4])[NH:5][C:6]1[CH:20]=[C:19]2[C:9](=[CH:8][CH:7]=1)[NH:10][C:11]([Br:21])=[C:12]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)Nc1ccc2[nH]cc(CCNC(C)=O)c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COC(=O)Nc1ccc2[nH]c(Br)c(CCNC(C)=O)c2c1

Procedure:
A solution of 5-methoxycarbonylamino-N-acetyltryptamine (0.05 mmol) in acetic acid (0.5 mL) is treated with N-bromosuccinimide (0.05 mmol) 3.5 h at 25° C. The solution is next neutralized with 50% sodium hydroxide solution and extracted with ethyl acetate. The organic extract is evaporated and the purified product obtained following chromatography on silica gel with 2% methanol-chloroform as eluent.