Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]([S:26]([CH3:29])(=[O:28])=[O:27])=[C:9]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[C:10]2[N:11]([C:13]([CH2:16][CH3:17])=[CH:14][CH:15]=2)[N:12]=1)(=O)=O.[O:32]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:16]([C:13]1[N:11]2[N:12]=[C:7]([C:33]3[O:32][CH:36]=[CH:35][CH:34]=3)[C:8]([S:26]([CH3:29])(=[O:27])=[O:28])=[C:9]([C:18]3[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=3)[C:24]#[N:25])[C:10]2=[CH:15][CH:14]=1)[CH3:17]
Reactant: CCc1ccc2c(-c3cccc(C#N)c3)c(S(C)(=O)=O)c(OS(=O)(=O)C(F)(F)F)nn12
Reactant: OB(O)c1ccoc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CCc1ccc2c(-c3cccc(C#N)c3)c(S(C)(=O)=O)c(-c3ccco3)nn12
Temperature: 85 °C
Reaction time: 0.33 h
Yield: 27.8 %

Procedure:
A mixture of 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[1,2-b]pyridazin-2-yl trifluoromethanesulfonate (50.0 mg), 3-furylboronic acid (23.6 mg), dichlorobis(triphenylphosphine)palladium (3.71 mg), and 2 N sodium carbonate (44.8 mg in 0.2 mL of water) in dioxane was stirred for 20 minutes at 85° C. The mixture was partitioned between EtOAc and water, and the organic layer was washed with brine, dried, and evaporated. Preparative thin layer chromatography (EtOAc-hexane=1-1) afforded 3-[7-ethyl-2-(2-furyl)-3-(methylsulfonyl)pyrrolo[1,2-b]pyridazin-4-yl]benzonitrile as an orange solid (11.5 mg).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.[CH:9]([N-]C(C)C)(C)C.[Li+].IC>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH3:9])[N:3]=1
Reactant: Cc1cccc(Br)n1
Reactant: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Product: CCc1cccc(Br)n1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 47.9 %

Procedure:
To a solution of 2-bromo-6-methylpyridine (302 mg, 1.76 mmol) an 10 mL THF at −78° C., was added a solution of lithium diisopropylamide (1.8 M in heptane/THF/ethylbenzene, 1.07 mL, 1.93 mmol). The bright orange/red mixture was treated with iodomethane (0.20 mL, 3.2 mmol). The mixture was stirred at −78° C. for 10 min, then was removed from the ice bath and stirred 30 min. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with water (2×) and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (0 to 20% EtOAc/hexanes gradient) to afford 157 mg of Intermediate 163.1 as a colorless oil. LCMS (2 min gradient) RT=1.26 min, 186.0 (M+H)+.
Reaction SMILES: [CH:1]1[C:6]([CH2:7][C@H:8]([NH2:12])[C:9]([OH:11])=[O:10])=[CH:5][C:4]([OH:13])=[C:3]([OH:14])[CH:2]=1.Cl.O.[CH2:17]=O.[OH-].[Na+]>O>[OH:13][C:4]1[CH:5]=[C:6]2[C:1](=[CH:2][C:3]=1[OH:14])[CH2:17][NH:12][C@H:8]([C:9]([OH:11])=[O:10])[CH2:7]2
Reactant: N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O
Reactant: C=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)[C@@H]1Cc2cc(O)c(O)cc2CN1
Temperature: 2.5 °C
Reaction time: 10 h
Yield: 95.4 %

Procedure:
To a cold (0-5° C.) suspension of Levodopa (197.2 g, 1.0 mol) in water (1.18 L) was added 32% aqueous HCl (159.5 g, 1.4 mol). The resulting solution was cooled to 0-5° C., and 37% formaldehyde water solution (243.24 g, 3.0 mol) was added. The resulting solution was allowed to warm to 20-25° C., and stirred at 20-25° C. for 10 h. The reaction solution was cooled to 0-5° C., and 2 N aqueous NaOH (700 mL, 1.4 mol) was slowly added to adjust pH to 5-5.5. White or light yellow solids precipitated during the addition. The resulting suspension was stirred at 0-5° C. for 2-3 h. The mixture was filtered, and rinsed with water (2×500 mL). The solids were dried under vacuum to give 199.52 g of a light yellow solid. Yield=95.3%.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[C:16]4=[N:17][C:18]([C:21](=O)[CH3:22])=[CH:19][N:20]=[C:15]4[N:14]=[N:13]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH:25]([C:27]([NH2:29])=[O:28])[NH2:26].C(N(CC)CC)C>CO>[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[C:16]4=[N:17][C:18](/[C:21](=[N:26]/[NH:25][C:27]([NH2:29])=[O:28])/[CH3:22])=[CH:19][N:20]=[C:15]4[N:14]=[N:13]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Reactant: NNC(N)=O
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: C/C(=N\NC(N)=O)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Temperature: 37 °C
Reaction time: 0.33 h
Yield: 60.2 %

Procedure:
To a solution of 1-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)ethanone (35 mg, 0.115 mmol) in MeOH (3 mL), was added hydrazinecarboxamide hydrochloride (115 mg, 1.035 mmol). The solution was heated to 37° C. overnight. Triethyl amine (1 mL) was added and the solution was stirred at rt for 20 min. Solvents were removed in vacuo and the residue was diluted with DCM, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford 25 mg of the title compound in 57% yield as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.90 (s, 1H), 9.85 (s, 1H), 8.89 (m, 1H), 3.36 (d, 1H), 8.01 (m, 2H), 7.82 (d, 1H), 7.53 (dd, 1H), 6.17 (s, 2H), 2.32 (s, 3H). LCMS (method A): [MH]+=384, tR=4.09 min.
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][CH:21]([N:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[C:40]#[N:41])=[CH:27][C:26]1=[O:42])[C:22]([OH:24])=O)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:43][C:44]1[CH:54]=[CH:53][C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:46][CH:45]=1.CC(C)N=C=NC(C)C>CN(C)C=O>[Si:1]([O:18][CH2:19][CH2:20][CH:21]([N:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[C:40]#[N:41])=[CH:27][C:26]1=[O:42])[C:22]([NH:43][C:44]1[CH:45]=[CH:46][C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:53][CH:54]=1)=[O:24])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: COc1cn(C(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C(=O)O)c(=O)cc1-c1cc(Cl)ccc1C#N
Agent: CC(C)N=C=NC(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(NC(=O)C(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)cc1

Procedure:
565 mg (940 μmol) of 4-{[tert-butyl(diphenyl)silyl]oxy}-2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid (racemate), 155 mg (940 μmol) of ethyl 4-aminobenzoate, 134 mg (940 μmol) of Oxima and 146 μl (940 μmol) of DIC in 19 ml of dimethylformamide were reacted according to General Method 5B. The crude product was purified by flash chromatography (120 g cartridge, 85 ml/min, cyclohexane/ethyl acetate gradient). Yield: 268 mg (38% of theory)
Reaction SMILES: Cl[CH2:2][C:3]1[C:4]2[N:5]([CH:9]=[CH:10][N:11]=2)[CH:6]=[CH:7][CH:8]=1.[OH:12][C:13]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:14]=1[CH:15]=[O:16].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:11]1[CH:10]=[CH:9][N:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][O:12][C:13]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:14]=3[CH:15]=[O:16])[C:4]=12
Reactant: COc1ccc(O)c(C=O)c1
Reactant: ClCc1cccn2ccnc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(OCc2cccn3ccnc23)c(C=O)c1
Temperature: 87.5 °C
Yield: 45 %

Procedure:
To a solution of the crude 8-(chloromethyl)imidazo[1,2-a]pyridine (6.8 mmol, 1 eq) and 2-hydroxy-5-methoxybenzaldehyde (1.3 g, 8.1 mmol, 1.2 eq) in DMF (20 mL) was added potassium carbonate (2.8 g, 20.4 mmol, 3 eq) and the reaction mixture was heated at 85-90° C. for 5 h. DMF was removed under vacuum and the residue was taken in ethyl acetate and filtered. The solid was washed with additional ethyl acetate, and then dried and evaporated to give the crude, which was purified by column chromatography (EtOAc/Hexane) to yield the desired compound in 45% yield. NMR (400 MHz, CDCl3): δ 3.80 (s, 3H), 5.60 (s, 2H), 6.85 (d, 1H), 7.12 (d, 2H), 7.36 (m, 2H), 7.66 (m, 2H), 8.14 (m, 1H), 10.58 (s, 1H); MS: exact mass calculated for C16H14N2O3, 282.10; m/z found, 283 [M+H]+.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:9]=2)[N:4]([C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.[CH3:35][C:36]1[CH:41]=[C:40](B(O)O)[CH:39]=[CH:38][N:37]=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>[CH3:35][C:36]1[CH:41]=[C:40]([C:2]2[NH:3][N:4]([C:16]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:5]3[C:10]=2[CH2:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7][CH:6]=3)[CH:39]=[CH:38][N:37]=1
Reactant: CCOC(=O)c1ccc2c(c1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1cc(B(O)O)ccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: CCOC(=O)C1=CC=C2C(=C(c3ccnc(C)c3)NN2C(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Temperature: 80 °C
Yield: 85 %

Procedure:
ethyl 3-bromo-1-trityl-1H-indazole-5-carboxylate (510 mg, 1.0 mol) was added to a vial containing 2-methylpyridin-4-ylboronic acid (128 mg, 1.04 mol) and tetrakis(triphenylphosphine)palladium (140 mg, 0.104 mol). After purging the vial with nitrogen gas, dioxane (5 mL) and 2M sodium carbonate (5 mL) was added to the vial respectively. The reaction mixture was stirred and was heated to 80° C. for overnight. Upon completion, the mixture was concentrated under vacuo. The mixture was extracted using ethyl acetate (3×100 mL). The extracts were combined and dried using anhydrous sodium sulfate. The resulting mixture was purified using flash chromatography to give the desired compound in 85% yield.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[N:8]=[CH:9][NH:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].C([O-])([O-])=O.[K+].[K+].[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>C1COCC1.O>[N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[N:8]([S:25]([C:22]3[CH:23]=[CH:24][C:19]([CH3:29])=[CH:20][CH:21]=3)(=[O:27])=[O:26])[CH:9]=[N:10][C:6]=2[CH:5]=1)([O-:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=[N+]([O-])c1ccc2nc[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2cnc3cc([N+](=O)[O-])ccc32)cc1
Reaction time: 16 h

Procedure:
To a stirring solution of 5-nitrobenzimidazole (7.5 g, 46 mmol) in THF (300 mL) and water (150 mL) was added K2CO3 (15.9 g, 115 mmol), followed by p-toluenesulfonyl chloride (11.4 g, 46 mmol). After stirring for 16 h, solvents were removed in vacuo and the residue was partitioned between ethyl acetate and water. The layers were separated and the organic phase was washed with brine, then dried with MgSO4, filtered and concentrated in vacuo. The crude solid was dissolved in choloroform and chromatographed over a silica gel column with a gradient of chloroform through 10% methanol/chloroform. The product containing fractions were combined and concentrated in vacuo to give 11.4 g (79%) of light yellow solid.
Reaction SMILES: [CH3:1][Si:2]([CH3:33])([CH3:32])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:8]1[N:13]2[N:14]=[CH:15][CH:16]=[C:12]2[N:11]=[C:10]([CH:17]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)[CH:9]=1.C1C(=O)N([I:41])C(=O)C1>CC#N>[CH3:29][Si:28]([CH3:31])([CH3:30])[CH2:27][CH2:26][O:25][CH2:24][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:33])([CH3:32])[CH3:1])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([I:41])=[C:12]2[N:11]=[C:10]([CH:17]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)[CH:9]=1
Reactant: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(C2CCC(=O)CC2)nc2ccnn12
Reactant: O=C1CCC(=O)N1I
Solvent: CC#N
Product: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(C2CCC(=O)CC2)nc2c(I)cnn12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.1 %

Procedure:
To a solution of 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone (775 mg, 1.58 mmol) in CH3CN (10 mL) was added NIS (391 mg, 1.74 mmol). The resulting solution was stirred at rt for 30 min before quenching with Na2S2O3 (sat.). CH3CN was removed under reduced pressure. The residue was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-20% EtOAc/Hexanes, Rf=0.3 in 20% EtOAc) to afford 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone as a pale yellow oil (751 mg).
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH:7]([N:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])[CH2:8]2)=[CH:4][CH:3]=1.[Li]C(C)(C)C.CCCCC.CN([CH:31]=[O:32])C>C(OCC)C>[CH2:12]([N:11]([CH2:15][CH2:16][CH3:17])[CH:7]1[CH2:8][C:9]2[C:5](=[CH:4][CH:3]=[C:2]([CH:31]=[O:32])[CH:10]=2)[CH2:6]1)[CH2:13][CH3:14]
Reactant: CCCN(CCC)C1Cc2ccc(Br)cc2C1
Reactant: CN(C)C=O
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: CCCCC
Product: CCCN(CCC)C1Cc2ccc(C=O)cc2C1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
Distilled (6-bromo-indan-2-yl)-dipropyl-amine (Example 11, 270 mg, 0.91 mmol) was dissolved in dry diethyl ether (20 mL). The solution was kept under argon and cooled to -78° C. A solution of t-BuLi in pentane 1.7M (0.7 mL, 1.20 mmol) was added and the mixture was stired at -78° C. for 1 h. Freshly distilled DMF (0.12 mL, 1.55 mmol) was added at -78° C. and the mixture was stirred at this temperature for 30 min. The reaction mixture was allowed to reach room temperature and stirred for additional 1 h. The organic layer was washed with aq. Na2CO3 (5%), the layers separated, dried (Na2CO3) and evaporated to dryness. MS m/e 245 (11, M+), 216 (100), 145 (17), 117 (22), 72 (21).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH:17]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(C(C)=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=1)[O:15][CH:17]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCC(Cl)c1ccccc1
Reactant: Oc1cccc(OCc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCOC(=O)CCC(Oc1cccc(OCc2ccccc2)c1)c1ccccc1
Yield: 17.1 %

Procedure:
A mixture of 3-benzyloxyphenol (3 g), ethyl (RS)-4-chloro-4-phenylbutanoate (4.53 g), potassium carbonate (4.14 g), potassium iodide (100 mg) and methyl ethyl ketone (100 mL) is heated at reflux for 40 hours. The mixture is evaporated to dryness and the residue is partitioned between ethyl acetate (200 mL) and water (200 mL). The organic layer is dried over magnesium sulphate, filtered, and concentrated in vacuo. Flash chromatography of the resulting oil, eluting with a mixture of ethyl acetate and cyclohexane (1:19 v/v), gives ethyl (RS)-4-(3-benzyloxyphenoxy)-4-phenylbutanoate (1 g), in the form of a yellow oil.
Reaction SMILES: B.[CH:2](=[C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]1=O)[CH3:3].CO.Cl>C1COCC1>[CH2:2]([CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH2:5]1)[CH3:3]
Reactant: CC=C1C(=O)Nc2ccccc21
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: CCC1CNc2ccccc21

Procedure:
Under a nitrogen atmosphere 41 mL (41 mmol) of a 1M borane in THF solution was added dropwise to 2.2 g (14 mmol) 3-ethylidene-1,3-dihydro-indol-2-one in 50 mL THF. The reaction mixture was refluxed for 3 h and then at 0° C. mixed with 10 mL methanol followed by 15 mL semi-concentrated hydrochloric acid solution. The reaction mixture was refluxed for 3 h with stirring, cooled and washed twice with ethyl acetate. The aqueous phase was made alkaline with aqueous 4M sodium hydroxide solution and extracted three times with ethyl acetate. The organic phases were combined, dried on sodium sulphate and evaporated down.
Reaction SMILES: C([O:5][C:6]([CH:8]1[CH:14]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[CH2:13][CH2:12][CH2:11][CH2:10][N:9]1[S:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)(=[O:22])=[O:21])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:17]([O:16][CH2:15][CH:14]1[CH2:13][CH2:12][CH2:11][CH2:10][N:9]([S:20]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)(=[O:22])=[O:21])[CH:8]1[C:6]([OH:7])=[O:5])(=[O:19])[CH3:18]
Reactant: COc1ccc(S(=O)(=O)N2CCCCC(COC(C)=O)C2C(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(S(=O)(=O)N2CCCCC(COC(C)=O)C2C(=O)O)cc1
Temperature: 25 °C

Procedure:
To a solution of 3-Acetoxymethyl-1-(4-methoxy-benzenesulfonyl)-azepane-2-carboxylic acid tert-butyl ester (266 mg, 0.6 mmoL) in 1.5 mL dichloromethane at 0° C. was added 1.5 mL of trifluoroacetic acid. The reaction was gradually allowed to warm to ambient temperature, and the solvent was removed under reduced pressure after 1.4 hours. The residue was azeotroped twice with toluene and purified by column chromatography (silica: 30% ethyl acetate in hexanes with 1% acetic acid to 4% methanol in dichloromethane with 1% acetic acid) to yield 3-Acetoxymethyl-1-(4-methoxy-benzenesulfonyl)-azepane-2-carboxylic acid quantitatively; MS: (M+H)+ =386, (M+NH4)+ =403.
Reaction SMILES: [CH3:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Br[CH2:17][CH2:18][CH2:19][CH2:20][C:21](OCC)([O:25]CC)[O:22][CH2:23][CH3:24].C(O)(=O)C>O1CCCC1>[CH2:23]([O:22][C:21]([CH2:20][CH2:19][CH2:18][CH2:17][CH2:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1)=[O:25])[CH3:24]
Reactant: Cc1cccc2cncn12
Reactant: CCOC(CCCCBr)(OCC)OCC
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCOC(=O)CCCCCc1cccc2cncn12
Reaction time: 0.29 h

Procedure:
5-Methylimidazo[1,5-a]pyridine [J. Org. Chem. 40, 1210 (1975), 424.7 g]is charged into a 12 liter flask equipped with mechanical stirrer, thermometer and nitrogen atmosphere. Dry tetrahydrofuran (THF, 3,000 ml) is charged into the flask and the resulting solution is cooled to -65° in a dry ice/acetone bath. n-Butyllithium (1.0 mole, 2.4 N in hexane) is poured into the flask all at once under a nitrogen atmosphere. The temperature rises to -32°. The mixture is recooled to -50° and a second mole of n-butyllithium is charged in the same manner. A second temperature rise occurs and after again cooling to -50°, a third mole of the n-butyl-lithium is charged into the reactor. The reaction mixture is then stirred for twenty minutes, the temperature drops to -65°. To this stirring solution a cold (-67°) solution of 5-bromo-1,1,1-triethoxypentane (606.9 g) in 500 ml of THF is added as rapidly as possible, raising the temperature to -25°. The reaction mixture is then warmed to -15° and stirred for 2 hours. Acetic acid (50 ml) is added and most of the solvent is removed under vacuum. The residue is taken up in 2,000 ml of ethyl ether; acetic acid (100 ml), and 12 N HCl (100 ml) are added while the reaction mixture is cooled to 0°. After 15 to 20 minutes, ice-cold 7.5 N ammonium hydroxide (1000 ml) is added. The organic phase is separated and the aqueous is washed again with ethyl ether (500 ml). The pH of the aqueous is adjusted to 9 with ammonium hydroxide and extracted again wth ethyl ether (500 ml). The combined ether extracts are washed with a dilute sodium chloride solution basified to pH 13-14 with potassium hydroxide. The ether extract is treated with charcoal and magnesium sulfate. The mixture is filtered and evaporated to give a dark oil which is dried at 2mm Hg. The oil is distilled under high vaccuum to give 5-(5-ethoxycarbonylpentyl)-imidazo[1,5-a]pyridine of Example 1, boiling at 220°/0.2 mm Hg.
Reaction SMILES: [H-].[Na+].[C:3]([Si:7]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[O:8][CH2:9][CH2:10][CH2:11][CH:12]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[OH:13])([CH3:6])([CH3:5])[CH3:4].[CH3:33]I>C1COCC1>[C:3]([Si:7]([O:8][CH2:9][CH2:10][CH2:11][CH:12]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[O:13][CH3:33])([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:6])([CH3:4])[CH3:5]
Reactant: CI
Reactant: CC(C)(C)[Si](OCCCC(O)c1ccc(Cl)cc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(CCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 100.9 %

Procedure:
To a suspension of NaH (153 mg 60% dispersed in mineral oil, 6.39 mmol) in 20 mL THF was slowly added at room temperature 4-(tert-butyl-diphenyl-silanyloxy)-1-(4-chloro-phenyl)-butan-1-ol (330 mg, 0.75 mmol) as a solution in 10 mL THF followed by the dropwise addition of methyl iodide (339 μL, 5.25 mmol). The reaction mixture was stirred for 3 h at room temperature before being quenched by the careful addition of saturated aqueous NH4Cl (30 mL). The mixture was extracted with ethylacetate (3×30 mL) and the combined organic layers washed with brine (2×20 mL) and dried over sodium sulfate. After evaporation of solvent the product was isolated by flash column chromatography eluting with 0% to 30% ethyl acetate/hexane to give 343 mg of the title compound as a colorless oil.
Reaction SMILES: CO.C[O-].[Na+].[C:6](I)([C:9]([C:12]([C:15]([C:18]([C:21]([C:24]([C:27]([F:30])([F:29])[F:28])([F:26])[F:25])([F:23])[F:22])([F:20])[F:19])([F:17])[F:16])([F:14])[F:13])([F:11])[F:10])([F:8])[F:7]>O>[CH:6]([C:9]([C:12]([C:15]([C:18]([C:21]([C:24]([C:27]([F:28])([F:29])[F:30])([F:25])[F:26])([F:22])[F:23])([F:20])[F:19])([F:17])[F:16])([F:14])[F:13])([F:11])[F:10])([F:8])[F:7]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: FC(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.7 %

Procedure:
Into a 500 cc four-necked equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer, 200 cc of methanol and 32.4 g (0.6 mol) of sodium methoxide were charged. The reactor was heated to bring the internal temperature to 60° C. Then, 273 g of (0.5 mol) of C8F17I was dropwise added thereto over a period of one hour. After completion of the dropwise addition, heating and refluxing were continued for 10 hours. The conversion at that time was 99.8%. The reactor was cooled to room temperature. Then, 300 g of water was added to dissolve precipitated potassium iodide. The crude reaction solution was separated into two layers, and the fluorocarbon layer (lower layer) was further washed with 300 g of water to obtain 201 g of C8F17H having a purity of 99.4%. In the reactor, no formation of tar was observed.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:18]=[CH:17][C:16]2[O:15][C:14]3[C:9](=[CH:10][C:11]([C:19](=[O:22])[CH2:20]Br)=[CH:12][CH:13]=3)[C:8](=[O:23])[C:7]=2[CH:6]=1)=[O:4].[CH2:24]([NH:26][CH2:27][CH3:28])[CH3:25]>O1CCCC1>[CH2:24]([N:26]([CH2:27][CH3:28])[CH2:2][C:3]([C:5]1[CH:18]=[CH:17][C:16]2[O:15][C:14]3[C:9](=[CH:10][C:11]([C:19](=[O:22])[CH2:20][N:26]([CH2:27][CH3:28])[CH2:24][CH3:25])=[CH:12][CH:13]=3)[C:8](=[O:23])[C:7]=2[CH:6]=1)=[O:4])[CH3:25]
Reactant: CCNCC
Reactant: O=C(CBr)c1ccc2oc3ccc(C(=O)CBr)cc3c(=O)c2c1
Solvent: C1CCOC1
Product: CCN(CC)CC(=O)c1ccc2oc3ccc(C(=O)CN(CC)CC)cc3c(=O)c2c1
Temperature: -20 °C

Procedure:
To a mixture of 2,7-bis(2-bromoacetyl)xanthen-9-one in tetrahydrofuran is added diethylamine, each cooled to -20°C. The reaction mixture is maintained at -20°C. for 24 hours then allowed to warm slowly to room temperature and then maintained at room temperature for 5 days. The mixture is filtered, and the filtrate evaporated to dryness. The resulting residue is dissolved in dilute HCl, filtered and the filtrate is made alkaline, keeping the temperature of the mixture around 0°C. The mixture is extracted with methylene chloride, and the extract acidified to Congo Red. The resulting solid is filtered off and recrystallized from methanol-diethylether to give the desired product.