Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7]([NH2:9])[S:8][C:4]=2[CH:3]=1.[CH3:12][O:13][C:14]1[CH:24]=[CH:23][C:17](/[CH:18]=[CH:19]/B(O)O)=[CH:16][CH:15]=1>>[CH3:12][O:13][C:14]1[CH:24]=[CH:23][C:17](/[CH:18]=[CH:19]/[C:2]2[CH:11]=[CH:10][C:5]3[N:6]=[C:7]([NH2:9])[S:8][C:4]=3[CH:3]=2)=[CH:16][CH:15]=1
Reactant: Nc1nc2ccc(Br)cc2s1
Reactant: COc1ccc(/C=C/B(O)O)cc1
Product: COc1ccc(/C=C/c2ccc3nc(N)sc3c2)cc1

Procedure:
Compound (E)-6-(4-methoxystyryl)benzo[d]thiazol-2-amine (W201) was prepared using the general procedure for Suzuki coupling reaction between 6-bromobenzo[d]thiazol-2-amine (69 mg, 0.3 mmol) and (E)-4-methoxystyrylboronic acid (53 mg, 0.3 mmol), as a white solid (80 mg, 94%). 1H NMR (400 MHz, DMSO-d6) δ 7.80 (d, J=1.6 Hz, 1 H), 7.46 (s, 2 H), 7.45 (d, J=8.8 Hz, 2 H), 7.36 (dd, J=8.4, 1.6 Hz, 1 H), 7.24 (d, J=8.0 Hz, 1 H), 7.03 (d, J=2.0 Hz, 2 H), 6.89 (d, J=9.2 Hz, 1 H), 3.71 (s, 3 H); MS (ESI) m/z 283 (M+H+).
Reaction SMILES: [I-].[CH3:2][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[CH2:28]([C:35]1[N:40]=[N:39][C:38]([N:41]2[CH2:46][CH2:45][N:44]([C:47]3[CH:52]=[N:51][C:50]([C:53](=O)[CH3:54])=[CH:49][N:48]=3)[C@H:43]([CH3:56])[CH2:42]2)=[C:37]([CH3:57])[C:36]=1[CH3:58])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[CH2:28]([C:35]1[N:40]=[N:39][C:38]([N:41]2[CH2:46][CH2:45][N:44]([C:47]3[CH:52]=[N:51][C:50]([C:53]([CH3:2])=[CH2:54])=[CH:49][N:48]=3)[C@H:43]([CH3:56])[CH2:42]2)=[C:37]([CH3:57])[C:36]=1[CH3:58])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(=O)c1cnc(N2CCN(c3nnc(Cc4ccccc4)c(C)c3C)C[C@H]2C)cn1
Agent: CC(C)(C)[O-]
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=C(C)c1cnc(N2CCN(c3nnc(Cc4ccccc4)c(C)c3C)C[C@H]2C)cn1
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 37.3 %

Procedure:
Methyltriphenylphosphonium iodide (410 mg, 1.010 mmol) is added to THF (5.5 mL) and cooled to 5° C. Potassium tert-butoxide (1.1 mL, 1M in THF, 1.1 mmol) is added dropwise and the reaction is stirred for 30 min. 1-[(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-yl]-ethanone (350 mg, 0.841 mmol) in THF (1.5 mL) is added to the reaction. The reaction is allowed to stir 1 h at 5° C., and then the ice bath is removed and the reaction is allowed to stir an additional 16 h at room temperature. Remove THF in vacuo. The residue is purified by flash chromatography on silica gel (60-90% EtOAc/heptane) to afford the title compound (130 mg, 37%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:7]=[C:8]([CH2:14]O)[CH:9]=[CH:10][C:11]=1[O:12][CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C(=O)N([Br:45])C(=O)C1>C(Cl)Cl>[Br:45][CH2:14][C:8]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:6]([O:5][C:4]2[CH:16]=[CH:17][CH:18]=[C:2]([Cl:1])[CH:3]=2)[CH:7]=1
Reactant: COc1ccc(CO)cc1Oc1cccc(Cl)c1
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1ccc(CBr)cc1Oc1cccc(Cl)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 91.6 %

Procedure:
To a solution of 3-(3-chloro-phenoxy)-4-methoxy-phenyl]-methanol (13) (315 mg, 1.2 mmol) and triphenylphosphine (390 mg, 1.5 mmol) in methylene chloride (5 ml) was added NBS (0.250 mg, 1.4 mmol) in portions at 0° C. under nitrogen. After 10 min of stirring at 0° C., the mixture was allowed to warm to room temperature, and continued to stir for 16 h. After the solvent was removed, the residue was purified by silica gel column chromatography with ether/hexane as eluent to give 360 mg (85% yield) of product (14).
Reaction SMILES: [CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([CH2:17][O:18][C:19]3[CH:20]=[N:21][C:22]([C:30]4[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:31]=4[F:38])=[C:23]([CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8]CC)=[O:7])[CH2:3][CH2:2]1.[OH-].[Na+].Cl>C1COCC1.CO>[CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([CH2:17][O:18][C:19]3[CH:20]=[N:21][C:22]([C:30]4[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:31]=4[F:38])=[C:23]([CH2:25][C:26]([CH3:29])([CH3:27])[CH3:28])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([OH:8])=[O:7])[CH2:2][CH2:3]1
Reactant: CCOC(=O)CC(c1cc(COc2cnc(-c3cc(OC)ccc3F)c(CC(C)(C)C)c2)ncn1)C1CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(F)c(-c2ncc(OCc3cc(C(CC(=O)O)C4CC4)ncn3)cc2CC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 103.1 %

Procedure:
To a solution of ethyl 3-cyclopropyl-3-(6-(((6-(2-fluoro-5-methoxyphenyl)-5-neopentylpyridin-3-yl)oxy)methyl)pyrimidin-4-yl)propanoate (362 mg) in THF (3.0 mL) and methanol (1.5 mL) was added 1N aqueous sodium hydroxide solution (3.0 mL), and the mixture was stirred at room temperature for 30 min. To the reaction mixture was added hydrochloric acid (1N, 3.0 mL) at room temperature, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After silica gel filtration, the solvent was evaporated under reduced pressure to give the title compound (353 mg) as a white amorphous solid.
Reaction SMILES: Br[CH2:2][C:3]1([CH3:16])[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([OH:30])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1>C1(C)C(C)=CC=CC=1>[NH2:14][C:9]1[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]2[O:4][C:3]([CH2:2][N:27]3[CH2:26][CH2:25][C:24]([C:21]4[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][CH:20]=4)([OH:30])[CH2:29][CH2:28]3)([CH3:16])[CH2:7][C:6]=2[C:8]=1[CH3:15]
Reactant: OC1(c2ccc(Cl)cc2)CCNCC1
Reactant: Cc1c(C)c2c(c(C)c1N)CC(C)(CBr)O2
Solvent: Cc1ccccc1C
Product: Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCC(O)(c3ccc(Cl)cc3)CC1)O2
Temperature: 120 °C
Reaction time: 1.5 h
Yield: 28.4 %

Procedure:
A suspension of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine (1.4 g) and 4-(4-chlorophenyl)-4-hydroxypiperidine (1.3 g) in xylene (10 mL) was stirred under nitrogen gas at 120° C. for 1.5 hours and, then, refluxed for 16 hours. Thereafter, 0.85 g of 4-(4-chlorophenyl)-4-hydroxypiperidine was added and the mixture was refluxed for 24 hours. After cooling, the reaction mixture was filtered and washed with diethyl ether. The filtrate was extracted with 1N-hydrochloric acid and the aqueous layer was made weakly acidic with saturated aqueous sodium hydrogen carbonate (NaHCO3). This aqueous layer was washed with diethyl ether and made weakly basic with saturated aqueous NaHCO3. This solution was extracted with ethyl acetate and the organic layer was washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was crystallized from diethyl ether/hexane to provide 0.58 g of the title compound. Yield 28%.
Reaction SMILES: [C:1]([C:5]1[O:6][CH:7]=[C:8]([CH2:10]Cl)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[P:12]([O:19]CC)([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15].C(OCC)(=O)C>C(OCC)(=O)C.C(O)C>[C:1]([C:5]1[O:6][CH:7]=[C:8]([CH2:10][P:12](=[O:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOP(OCC)OCC
Reactant: CC(C)(C)c1nc(CCl)co1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOP(=O)(Cc1coc(C(C)(C)C)n1)OCC
Temperature: 160 °C
Reaction time: 16 h
Yield: 99.9 %

Procedure:
A mixture of 2-tert-butyl-4-chloromethyl-1,3-oxazole (10.42 g) and triethyl phosphite (19.94 g) was stirred at 160° C. for 16 hrs. Excess triethyl phosphite was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:1, v/v), ethyl acetate, then ethyl acetate-ethanol (10:1, v/v) to give diethyl [(2-tert-butyl-1,3-oxazol-4-yl)methyl]phosphonate as a colorless oil (16.51 g, yield 100%).
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[N:8]([CH:16]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:7]=1.[NH2:23][C:24]1[N:29]=[CH:28][C:27]([N:30]2[C:35](=[O:36])[CH2:34][C@H:33]3[CH2:37][N:38](C(OC(C)(C)C)=O)[CH2:39][C@H:32]3[CH2:31]2)=[CH:26][CH:25]=1>>[CH:16]1([N:8]2[C:6]3[N:7]=[C:2]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([N:30]5[C:35](=[O:36])[CH2:34][C@H:33]6[CH2:37][NH:38][CH2:39][C@H:32]6[CH2:31]5)=[CH:28][N:29]=4)[N:3]=[CH:4][C:5]=3[CH:10]=[C:9]2[C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: CC(C)(C)OC(=O)N1C[C@@H]2CC(=O)N(c3ccc(N)nc3)C[C@@H]2C1
Reactant: CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCCCC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4C[C@@H]5CNC[C@@H]5CC4=O)cn3)nc2n1C1CCCCCC1
Yield: 86 %

Procedure:
Following general N—C coupling procedure 1, 2-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide and cis-tert-butyl 5-(6-aminopyridin-3-yl)-6-oxohexahydro-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate were combined and gave after purification cis-tert-butyl 5-(6-(7-cycloheptyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl)-6-oxohexahydro-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (85 mg) in 86% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.77 (s, 1H), 8.66 (d, J=9.09 Hz, 1H), 8.48 (br s, 1H), 8.24 (s, 1H), 7.64 (dd, J1=9.09 Hz, J2=2.53 Hz, 1H), 6.45 (s, 1H), 4.53 (m, 1H), 3.84 (dd, J1=13.14 Hz, J2=5.56 Hz, 1H), 3.70 (m, 3H), 3.31 (m, 2H), 3.17 (s, 6H), 2.82 (m, 3H), 2.63 (m, 2H), 2.51 (dd, J1=16.42 Hz, J2=5.81 Hz, 1H), 2.01 (m, 2H), 1.87 (m, 2H), 1.73 (m, 4H), 1.58 (m, 2H), 1.48 (s, 9H). LCMS m/z 617.7 (M+H)+.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].[Br:10][CH2:11][CH2:12][CH2:13]Br>>[Br:10][CH2:11][CH2:12][CH2:13][O:9][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1]
Reactant: Oc1cccc(F)c1F
Reactant: BrCCCBr
Product: Fc1cccc(OCCCBr)c1F

Procedure:
Analogously to Example 91b, 2.00 g of 2,3-difluorophenol and 30.7 g of 1,3-dibromopropane are reacted. The title compound is obtained as a colourless oil. Rf=0.39 (1:10 EtOAc-heptane); Rt=4.82.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:10][CH2:11][C:12]#C)[C:5]([F:9])=[C:6]([F:8])[CH:7]=1.[F-].[Cs+].[CH2:16](N(CC)C1C=CC=CC=1)C>CC(OC)(C)C>[Br:1][C:2]1[C:3]2[CH:16]=[C:11]([CH3:12])[O:10][C:4]=2[C:5]([F:9])=[C:6]([F:8])[CH:7]=1
Reactant: CCN(CC)c1ccccc1
Reactant: C#CCOc1cc(Br)cc(F)c1F
Agent: [Cs+]
Agent: [F-]
Solvent: COC(C)(C)C
Product: Cc1cc2c(Br)cc(F)c(F)c2o1

Procedure:
51.9 g (0.21 mol) of 5-bromo-1,2-difluoro-3-prop-2-ynyloxybenzene are heated at 205° C. for 4 h together with 20.7 g (0.14 mol) of caesium fluoride in 300 ml of N,N-diethylaniline. The batch is diluted with MTBE and washed a number of times with 1 N HCl. The solution is dried using sodium sulfate and concentrated to dryness. The residue is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=3:1), giving 4-bromo-6,7-difluoro-2-methylbenzofuran as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([NH2:15])=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1.[F:17][C:18]([F:23])([F:22])[C:19](O)=O>Cl>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=2)=[CH:6][C:5]2[NH:15][C:19]([C:18]([F:23])([F:22])[F:17])=[N:16][C:4]=2[CH:3]=1
Reactant: Nc1cc(Cl)c(-c2ccc(F)cc2)cc1N
Reactant: O=C(O)C(F)(F)F
Agent: Cl
Product: Fc1ccc(-c2cc3[nH]c(C(F)(F)F)nc3cc2Cl)cc1
Yield: 38 %

Procedure:
To a solution of 5-chloro-4-iodo-2-nitroaniline (5 g, 16.75 mmol) in dioxane (200 ml) was added (4-fluorophenyl)boronic acid (4.7 g, 33.59 mmol), water (20 ml), K3PO4 (7 g, 32.98 mmol), Pd(PPh3)4 (924 mg, 0.80 mmol) with an inert atmosphere of nitrogen. The resulting solution was stirred for 8 h at 95° C. and then concentrated under reduced pressure to give a residue, which was purified by a silica gel column with 5% to 20% ethyl acetate in petroleum ether to produce 5-chloro-4-(4-fluorophenyl)-2-nitroaniline as a yellow solid (4.1 g, 91%). Next, a solution of 5-chloro-4-(4-fluorophenyl)-2-nitroaniline (4.1 g, 15.38 mmol) in ethanol (100 ml) was added to hydrogen chloride (4 ml, 48 mmol, conc) and Zn (6 g, 460 mmol) at room temperature. The resulting solution was stirred for 3 h at 85° C. The resulting mixture was concentrated under vacuum and dissolved in water (200 ml), adjusted pH to 8 with aqueous sodium bicarbonate and extracted with dichloromethane (3×200 ml). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a residue, which was purified by a silica gel column with 5% to 10% ethyl acetate in petroleum ether to produce 4-chloro-5-(4-fluorophenyl)benzene-1,2-diamine as a brown oil (2.5 g, 70%). Finally, a solution of 4-chloro-5-(4-fluorophenyl)benzene-1,2-diamine (100 mg, 0.42 mmol) in hydrogen chloride (1 ml) and trifluoroacetic acid (5 ml) was stirred overnight at 80° C. The reaction was quenched by the addition of water (50 ml) and the pH value of the solution adjusted to 7 with aqueous sodium bicarbonate. The resulting solution was extracted with ethyl acetate (3×50 ml) and the organic layers combined and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a residue, which was purified by Pre-TLC with 10% ethyl acetate in petroleum ether to produce 5-chloro-6-(4-fluorophenyl)-2-(trifluoromethyl)-1H-1,3-benzodiazole as a white solid (50.7 mg, 38%).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([B:11]1[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]1)=[CH:7]2.[CH3:20]C1C2C(=CC=CC=2)NC=1>>[CH3:20][C:7]1[C:6]2[C:10](=[CH:2][CH:3]=[CH:4][CH:5]=2)[NH:9][C:8]=1[B:11]1[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]1
Reactant: Cc1c[nH]c2ccccc12
Reactant: CC1(C)OB(c2cc3cccc(Cl)c3[nH]2)OC1(C)C
Product: Cc1c(B2OC(C)(C)C(C)(C)O2)[nH]c2ccccc12

Procedure:
Prepared according to a procedure analogous to that described for 7-chloro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole using 3-methyl-1H-indole.
Reaction SMILES: N.[Li].[CH2:3]([OH:7])[CH2:4][C:5]#[CH:6].Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>O1CCCC1>[CH2:3]([OH:7])[CH2:4][C:5]#[C:6][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCBr
Reactant: C#CCCO
Agent: N
Agent: [Li]
Solvent: C1CCOC1
Product: CCCCCCCCC#CCCO
Temperature: 0 °C

Procedure:
To a mixture of 500 ml of anhydrous ammonia and 100 mg of ferric nitrate in a 2 liter three necked flask equiped with a mechanical stirrer and dry ice condenser was added 3.12 g of lithium wire in small portions. When the blue color had discharged, 14.0 g of 3-butyn-1-ol in 100 ml of tetrahydrofuran was added over 15 minutes and the reaction mixture refluxed for 1 hour. A solution of 34.5 ml of 1-bromooctane in 200 ml of tetrahydrofuran was added and the reaction mixture was allowed to reflux for 90 minutes. At the end of this period the entire reaction mixture was poured onto 1 liter of ice and then saturated with salt. The resulting aqueous solution was extracted twice with 500 ml of ether and the combined ethereal solutions were washed with brine and dried over potassium carbonate. The ether was evaporated and the residue distilled to give 25.13 g of 3-dodecyn-1-ol, b.p. 87°-90° /0.5 mm.
Reaction SMILES: [CH2:1]([Si:5]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:6](O)[CH2:7][CH:8]([CH3:10])[CH3:9])[CH2:2][CH:3]=[CH2:4].CS(Cl)(=O)=O.[N-:29]=[N+:30]=[N-:31].[Na+]>C(Cl)Cl.CCN(CC)CC>[N:29]([CH:6]([Si:5]([CH2:1][CH2:2][CH:3]=[CH2:4])([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:7][CH:8]([CH3:9])[CH3:10])=[N+:30]=[N-:31]
Reactant: [N-]=[N+]=[N-]
Reactant: C=CCC[Si](c1ccccc1)(c1ccccc1)C(O)CC(C)C
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CCC[Si](c1ccccc1)(c1ccccc1)C(CC(C)C)N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 87 %

Procedure:
To a solution of 34 (1.68 g, 5.16 mmol) in CH2Cl2 (100 mL) and Et3N (3.6 mL) at 0° C. was added dropwise over 5 min methanesulfonyl chloride (2.96 g, 25.8 mmol), and the solution was allowed to warm to rt over 1 h. After stirring overnight under argon, the mixture was cooled to 0° C. and quenched with water (50 mL). The organic layer was isolated and the aqueous layer extracted twice with 20-mL portions of CH2Cl2. The combined organic extracts were concentrated in vacuo at rt. The crude mesylate was dissolved in DMF (100 mL), and to this solution was added sodium azide (1.68 g, 25.8 mmol). After stirring for 8 h at rt, the mixture was partitioned between water (200 mL) and EtOAc (200 mL). The organic layer was isolated and aqueous layer extracted twice with 50-mL portions of EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated. Flash chromatography over silica gel (1/9 EtOAc:hexane) gave pure 35 as a colorless oil (1.57 g, 87%): Rf=0.90 (1/9 EtOAc:hexane); 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J=6.7 Hz, 4H), 7.41 (m, 6H), 5.88 (m, 1H), 5.00 (dd, J=17.0, 1.5 Hz, 1H), 4.92 (dd, J=10.2, 1.5 Hz, 1H), 3.44 (d, J=12.4 Hz, 1H), 2.12 (m, 2H), 1.84 (m, 1H), 1.60 (t, J=12.5 Hz, 1H), 1.30 (m, 3H), 0.92 (d, J=6.7 Hz, 3H), 0.89 (d, J=6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 140.7, 135.3, 132.6, 129.9, 128.0, 113.3, 49.2, 38.8, 27.5, 25.9, 23.3, 20.7, 10.5; IR (neat) 3071 (w), 3051 (w), 2995 (w), 2957 (s), 2923 (m), 2866 (m), 2102 (s), 1642 (w), 1473 (w), 1432 (s), 1264 (m), 1188 (w), 1116 (s), 1004 (w), 915 (m), 743 (s), 701 (s) cm−1; MS (FAB) m/e (rel. intensity) 350 (MH+, 18), 323 (32), 322 (100), 321 (27), 320 (16), 315 (42), 306 (42), 252 (17), 251 (23), 237 (18), 236 (73), 223 (26), 208 (17); HRMS (FAB) calcd for C11H28N3Si: 350.2053, found: 350.2040. Anal. Calcd for C21H27N3Si: C, 72.16; H, 7.79; N, 12.02. Found: C, 71.99; H, 7.91; N, 11.60.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH:23]=1)C1C=CC=CC=1.[H][H]>[Pd].C(O)C.O1CCCC1>[CH3:24][N:21]1[CH2:20][CH2:19][CH:18]([C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[C:9]([OH:8])[CH:10]=3)[NH:14][CH:13]=2)[CH2:23][CH2:22]1
Reactant: CN1CC=C(c2c[nH]c3ccc(OCc4ccccc4)cc23)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CN1CCC(c2c[nH]c3ccc(O)cc23)CC1
Yield: 51.1 %

Procedure:
A mixture of 5-benzyloxy-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (16.4 g, 51.5 mmol) and 5% palladium on carbon (4.0 g) in ethanol (125 mL) and tetrahydrofuran (125 mL) was hydrogenated with an initial hydrogen pressure of 60 psi (413 kPa) at ambient temperature for 16 h. The reaction mixture was filtered and concentrated under reduced pressure. The residue was crystallized from methanol and THF to give 6.06 g (51%) of the title compound as white crystals: mp=234-237° C.; MS(m/e): 230 (M+); Calculated for C14H18N2O: Calcd: C, 73.01; H, 7.88; N, 12.16. Found: C, 72.79; H, 8.17; N, 12.33.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][N:15]=[N:14][CH:13]=3)[CH2:9][C:8](=[O:18])[NH:7][C:6]=2[CH:19]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]>>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]=[C:10]([C:12]4[CH:17]=[CH:16][N:15]=[N:14][CH:13]=4)[CH2:9][C:8](=[O:18])[NH:7][C:6]=3[CH:19]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]
Reactant: COc1ccc(B(O)O)cc1OC
Reactant: O=C1CC(c2ccnnc2)=Nc2ccc(Br)cc2N1
Product: COc1ccc(-c2ccc3c(c2)NC(=O)CC(c2ccnnc2)=N3)cc1OC

Procedure:
The title compound was prepared from 8-bromo-4-(pyridazin-4-yl)-1H-benzo[b][1,4]diazepin-2(3H)-one (Example 1; 1 mmol) and commercial available 3,4-dimethoxyphenylboronic acid (CAS-No: 122775-35-3; 1.5 mmol) according to the general procedure G. Obtained as a yellow solid (75%), MS (EI) 375 [(M+1)+].
Reaction SMILES: Br[C:2](Br)=[CH:3][CH2:4][CH2:5][Si:6]([CH3:9])([CH3:8])[CH3:7].[Li]CCCC.[CH2:16]=[O:17].[NH4+].[Cl-]>C1COCC1>[CH3:7][Si:6]([CH3:9])([CH3:8])[CH2:5][CH2:4][C:3]#[C:2][CH2:16][OH:17]
Reactant: C[Si](C)(C)CCC=C(Br)Br
Reactant: C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: C[Si](C)(C)CCC#CCO
Temperature: -78 °C
Reaction time: 1 h
Yield: 83.7 %

Procedure:
To a flame dried flask was added (4,4-dibromo-but-3-enyl)trimethylsilane (3.43 g, 12 mmol). Dry THF (150 mL) was added and the mixture was cooled to −78° C. BuLi 1.6N in hexanes (24 mmol, 15 mL) was added and the mixture was stirred 1 h at −78° C., warmed to 22° C., and stirred for an additional 1 h. Finally, paraformaldehyde (1.4 g) was added and the mixture was refluxed. After 3.5 h the reaction was cooled to 22° C. and sat. NH4Cl (50 mL) was added. The contents of the flask were transferred to a separatory funnel and extracted with ether (3×200 mL). The organic layer was dried (Na2SO4), filtered and evaporated to give a crude yellow oil. Flash chromatography on silica gel (pentane/ether 5:1) afforded 1.57 g (84%) of 5-trimethylsilanylpent-2-yn-1-ol: IR (neat, cm−1) 3350, 2953, 2219, 1436, 1412, 1318, 1249, 1178, 1124, 1015, 905, 853; 1H NMR (300 MHz, CDCl3) δ−0.003 (s, 9 H), 0.76 (t, J=8 Hz 2 H), 1.75 (s, 1 H), 2.20-2.24 (m, 2 H), 4.21 (br s, 2 H); 13C NMR (75 MHz, CDCl3) δ−1.3, 13.8, 16.4, 51.7, 78.2, 88.9; HRMS (EI) ml/z calcd for C7H13OSi (M-CH3) 141.0736, found 141.0733 LRMS (EI) m/z 141 (M-CH3), 123, 113, 103, 97, 91, 85, 75, 66, 59.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH3:18])=[O:5])[CH3:2].[Br:19]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH2:18][Br:19])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1sc(Oc2ccccc2)nc1C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1sc(Oc2ccccc2)nc1CBr
Temperature: 25 °C
Yield: 101.9 %

Procedure:
A mixture of 4-methyl-2-phenoxy-thiazole-5-carboxylic acid ethyl ester (1.31 g, 4.99 mmol), N-bromosuccinimide (905 mg, 5.08 mmol) and benzoyl peroxide (60 mg, 0.25 mmol) in carbon tetrachloride (25 mL) was refluxed for 3 h before it was cooled to room temperature and partitioned between dichloromethane and water, the organic layer was washed with saturated aqueous sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound as a yellow solid (1.74 g): MS: (+) m/z 342.0, 344.0 (M+1, 79Br/81Br).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:15]3[C:11](=[N:12][N:13]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[O:33][CH3:34])[C:14]=3[CH:24]([CH3:26])[CH3:25])[C:10]2=[O:35])[CH:5]=[CH:6][C:7]=1[F:8].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:46](Br)[CH:47]=[CH2:48]>>[CH2:48]([C:16]1([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[C:15]2[C:11](=[N:12][N:13]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[O:33][CH3:34])[C:14]=2[CH:24]([CH3:26])[CH3:25])[C:10](=[O:35])[N:9]1[C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[CH:47]=[CH2:46]
Reactant: COc1ccccc1-n1nc2c(c1C(C)C)C(c1ccc(Cl)cc1)N(c1ccc(F)c(Cl)c1)C2=O
Reactant: C=CCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Product: C=CCC1(c2ccc(Cl)cc2)c2c(nn(-c3ccccc3OC)c2C(C)C)C(=O)N1c1ccc(F)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The title compound was prepared in analogy to the procedure described for example 74 but using the compound prepared in example 88, 2 equivalents of KHMDS and 2 equivalents of allyl bromide. The reaction mixture was stirred for 1 h at rt and quenched by addition of a saturated solution of ammonium chloride. The crude material was purified by silica gel column chromatography (hexane/EtOAc, 4:1). tR: 6.90 min (HPLC 2); ESI-MS: 550.1 [M+H]+ (LC-MS 2); Rf=0.55 (hexane/EtOAc, 1:1).