Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:8][C:9]1[C:14]2[C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[CH:16][S:17][C:13]=2[C:12](Br)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([NH:8][C:9]1[C:14]2[C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[CH:16][S:17][C:13]=2[C:12]([C:30]2[CH:31]=[CH:32][C:27]([CH3:26])=[CH:28][CH:29]=2)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2csc3c(Br)cnc(NCc4ccccc4)c23)cc1
Reactant: Cc1ccc(B(O)O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Product: Cc1ccc(-c2cnc(NCc3ccccc3)c3c(-c4ccc(C)cc4)csc23)cc1
Temperature: 150 °C
Yield: 53.5 %

Procedure:
A microwave reaction vessel was charged with benzyl-(7-bromo-3-p-tolyl-thieno[3,2-c]pyridin-4-yl)amine (20.0 mg, 0.0489 mmol), 4-methylphenylboronic acid (6.6 mg, 0.0489 mmol), palladium (II) acetate (1.0 mg, 0.00489 mmol), triphenylphosphine (3.8 mg, 0.0147 mmol) and sodium carbonate (15.5 mg, 0.147 mmol). The reaction was solvated in DME (0.75 ml) and distilled water (0.25 ml), the tube sealed, and set to stir in a Biotage microwave reactor. The reaction was heated at 150° C. for 1 h. At which point the reaction was allowed to cool to room temperature and further diluted with distilled water (10 ml). The aqueous phase was then extracted with DCM (2×20 ml), dried (MgSO4), filtered and the solvent removed in vacuo. The crude residue was subjected to flash column chromatography (eluent petroleum spirit 40-60° C.:EtOAc, 10:1, Rf 0.3). This afforded the title compound as a yellow solid (11.0 mg, 53%).
Reaction SMILES: [CH3:1][S:2]([O:5][C:6]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([C:17]2[N:18]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:19]3[C:24]([CH:25]=2)=[CH:23][C:22]([CH:26]=O)=[CH:21][CH:20]=3)=[C:11]2[C:7]=1[CH2:8][NH:9][C:10]2=[O:35])(=[O:4])=[O:3].[CH3:36][O:37][CH2:38][CH2:39][NH2:40].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C>[CH3:1][S:2]([O:5][C:6]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([C:17]2[N:18]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[C:19]3[C:24]([CH:25]=2)=[CH:23][C:22]([CH2:26][NH:40][CH2:39][CH2:38][O:37][CH3:36])=[CH:21][CH:20]=3)=[C:11]2[C:7]=1[CH2:8][NH:9][C:10]2=[O:35])(=[O:3])=[O:4]
Reactant: COc1cc(-c2cc3cc(C=O)ccc3n2C(=O)OC(C)(C)C)c2c(c1OS(C)(=O)=O)CNC2=O
Reactant: COCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC#N
Product: COCCNCc1ccc2c(c1)cc(-c1cc(OC)c(OS(C)(=O)=O)c3c1C(=O)NC3)n2C(=O)OC(C)(C)C
Yield: 55.8 %

Procedure:
In a similar manner to Step 2 of Example 6, 4-methanesulfonyloxy-5-methoxy-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (1.02 g, 2.66 mmol) was dissolved in acetonitrile (13.0 mL), and the solution was treated with 2-methoxyethylamine (3.47 mL, 39.9 mmol), acetic acid (2.28 mL, 13.3 mmol) and sodium triacetoxyborohydride (2.82 g, 39.9 mmol), followed by purification by flash column chromatography (chloroform/methanol=4/1) to obtain 4-methanesulfonyloxy-5-methoxy-7-[1-(tert-butoxycarbonyl)-5-(2-methoxyethylaminomethyl)indol-2-yl]isoindolinone (0.83 g, 56%).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][O:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2.S(O[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1)(=O)(=O)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(#N)C>[CH3:34][O:33][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=1)[CH2:26][CH2:25][N:2]([CH2:3][CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][O:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2)[CH3:1]
Reactant: COc1cccc(CCOS(C)(=O)=O)c1
Reactant: CNCCN1c2ccccc2COc2ccccc21
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: COc1cccc(CCN(C)CCN2c3ccccc3COc3ccccc32)c1
Temperature: 90 °C

Procedure:
5,11-Dihydro-5-[2-(N-methylamino)ethyl]dibenzo[b,e][1,4]oxazepine (349 mg, 1.37 mmol), 3-methoxyphenethyl mesylate (450 mg, 1.96 mmol), sodium carbonate (208 mg, 1.96 mmol) and sodium iodide (20 mg, 0.13 mmol) were added to acetonitrile (25 ml), and they were heated under reflux at 90° C. for 6 hours. The solvent was evaporated under reduced pressure. The obtained residue was distributed in ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with water and then dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was subjected to silica gel column chromatography. The product was eluted with dichloromethane and hexane (1:2) and then with dichloromethane as the eluent. The appropriate fractions were combined, and the solvent was evaporated under reduced pressure to obtain 5,11-dihydro-5-[2-[N-(3-methoxyphenethyl)-N-methylamino]ethyl]dibenzo[b,e][1,4]oxazepine in the form of a light yellow oil (275 mg, 52%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7]([CH3:13])([CH3:12])[CH:6]=[C:5]2[N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16].I[CH2:21][CH2:22][CH3:23]>>[CH2:21]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7]([CH3:13])([CH3:12])[CH:6]=[C:5]2[N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])[CH2:22][CH3:23]
Reactant: CN(C1=CC(C)(C)Oc2ccc(O)cc21)S(C)(=O)=O
Reactant: CCCI
Product: CCCOc1ccc2c(c1)C(N(C)S(C)(=O)=O)=CC(C)(C)O2

Procedure:
Similar to Example 8b, 0.5 g of N-(6-hydroxy-2,2-dimethyl-2H-chromen-4-yl)-N-methyl-methanesulfonamide was alkylated with 1 -iodopropane, giving 0.36 g of N-(6-propoxy-2,2-dimethyl-2H-chromen-4-yl)-N-methyl-methanesulfonamide; m.p. 93-95° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH2:11])[N:10]=2)[CH:7]=1.[H-].[Na+].Cl[C:15]1[CH:20]=[C:19]([CH2:21][N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:18]=[CH:17][N:16]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:17]3[CH:18]=[C:19]([CH2:21][N:22]4[CH2:23][CH2:24][CH2:25][CH2:26]4)[CH:20]=[CH:15][N:16]=3)[N:10]=2)[CH:7]=1
Reactant: Clc1cc(CN2CCCC2)ccn1
Reactant: Nc1cn2cc(Br)ccc2n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Brc1ccc2nc(Nc3cc(CN4CCCC4)ccn3)cn2c1
Temperature: 25 °C
Yield: 31.4 %

Procedure:
To a solution of 6-bromoimidazo[1,2-a]pyridin-2-amine (200 mg; 0.94 mmol) in dry THF (4 mL) was added NaH (90 mg; 3.76 mmol) in portions at 0° C. The reaction mixture was stirred at r.t. for half an hour. Then 2-chloro-4-(pyrrolidin-1-ylmethyl)pyridine (222 mg, 1.1 mmol) was added. The mixture was heated to 120° C. for 24 hrs. The mixture was quenched by addition of H2O (20 mL) slowly at 0° C., extracted with DCM (30 mL×3). The combined organic phases were concentrated under reduced pressure and purified by column chromatography on silica (DCM:MeOH=15:1) to obtain 6-bromo-N-(4-(pyrrolidin-1-ylmethyl)pyridin-2-yl)imidazo[1,2-a]pyridin-2-amine (110 mg, yield 80%) as a brown solid.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][CH:6]=1.S(=O)(=O)(O)O.O.[CH2:16](O)[CH3:17]>>[Br:1][C:2]1[S:3][C:4]([C:7]([O:9][CH2:16][CH3:17])=[O:8])=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccc(Br)s1
Reactant: CCO
Agent: O=S(=O)(O)O
Solvent: O
Product: CCOC(=O)c1ccc(Br)s1

Procedure:
2-Bromo-5-thiophenecarboxylic acid (500 mg) was dissolved in ethanol (5 mL), conc. sulfuric acid (50 μL) was added and the mixture was heated under reflux for 4 hrs. Conc. sulfuric acid (50 μL) was further added and the mixture was heated under reflux for 5 hrs. Then, the mixture was allowed to return to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and hexane as an eluent. The solvent was evaporated from the eluent to give the title compound (500 mg) as a yellow oil.
Reaction SMILES: [C:1]([C:5]1[C:6](=[O:27])[CH2:7][CH:8]([C:12]2[C:17]([CH3:18])=[C:16]([CH2:19][C:20]#[N:21])[C:15]([CH3:22])=[C:14]([C:23](=[O:25])[CH3:24])[C:13]=2[CH3:26])[CH2:9][C:10]=1[OH:11])(=[O:4])[CH2:2][CH3:3].[OH-:28].[Na+]>>[C:1]([C:5]1[C:6](=[O:27])[CH2:7][CH:8]([C:12]2[C:17]([CH3:18])=[C:16]([CH2:19][C:20](=[O:28])[NH2:21])[C:15]([CH3:22])=[C:14]([C:23](=[O:25])[CH3:24])[C:13]=2[CH3:26])[CH2:9][C:10]=1[OH:11])(=[O:4])[CH2:2][CH3:3]
Reactant: [OH-]
Reactant: CCC(=O)C1=C(O)CC(c2c(C)c(CC#N)c(C)c(C(C)=O)c2C)CC1=O
Agent: [Na+]
Product: CCC(=O)C1=C(O)CC(c2c(C)c(CC(N)=O)c(C)c(C(C)=O)c2C)CC1=O
Yield: 65 %

Procedure:
A solution of 2-propionyl-3-hydroxy-5-(3-acetyl-5-cyanomethyl-2,4,6-trimethylphenyl)cyclohex-2-en-1-one (0.67 g, 1.83 mmol) in 5% aqueous sodium hydroxide (12 ml) was refluxed for 30 min. The solution was then cooled, acidified and extracted with ethylacetate. The organic layer was washed with water, saturated aqueous sodium hydrogen carbon solution, further water then dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure to yield 2-propionyl-3-hydroxy-5-(3-acetyl-5-carbamoylmethyl-2,4,6-trimethylphenyl)cyclohex-2-en-1-one as a colourless solid (0.49 g, 65%). The compound was characterized by proton magnetic resonance spectroscopy (CDCl3 ; δ in ppm): 1.14 (3H,t); 2.13 (3H,s); 2.22 (3H,s); 2.32 (3H,s); 2.46 (3H,s); 2.4-3.9 (7H, m); 3.61 (2H,s); 5.48 (1H,brs); 6.10 (1H,brs); 18.00 (1H,brs). The sodium hydrogen carbonate solution washings were acidified and extracted with ethylacetate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure to yield 2-[3-(4-propionyl-5-hydroxycyclohex-3-one-4- enyl)-5-acetyl-2,4,6-trimethylphenyl]acetic acid (0.11 g, 16%) as a colourless solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[O:28][C:29]=3[CH3:30])=[CH:19][CH:18]=2)[N:5]=1)[CH3:2].[OH-].[Na+].O1CCCC1.C(O)C>Cl>[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[O:28][C:29]=3[CH3:30])=[CH:21][CH:22]=2)[N:5]=1)[CH3:2]
Reactant: CCOC(=O)CCc1cn(Cc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)nc1OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOc1nn(Cc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)cc1CCC(=O)O
Temperature: 25 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
A mixture of ethyl 3-[3-ethoxy-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazole-4-yl]propionate (441 mg), 1 N aqueous sodium hydroxide solution (2 ml), tetrahydrofuran (4 ml), and ethanol (4 ml) was stirred at room temperature for two hours, diluted with 1 N hydrochloric acid (2 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The obtained colorless crystals were collected by filtration, and 3-[3-ethoxy-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acid was obtained (328 mg, yield: 79%). This was recrystallized from ethanol-hexane. Melting point: 96–97° C.
Reaction SMILES: [Mg].Br[C:3]1[CH:4]=[C:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1.[CH3:10][N:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1.[Cl-].[NH4+]>CCOCC>[CH3:10][N:11]1[CH2:16][CH2:15][C:14]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[CH:4]=2)([OH:17])[CH2:13][CH2:12]1
Reactant: Cc1cccc(Br)c1
Reactant: CN1CCC(=O)CC1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: Cc1cccc(C2(O)CCN(C)CC2)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a layer of magnesium (24.3 g) covered with dry ether, a solution of m-bromotoluene (171 g, 1 mole) in dry ether (500 ml) is added under an atmosphere of nitrogen. After the addition, the mixture is heated at reflux for an hour, cooled to 0° C. and a solution of 1-methyl-4-piperidone (108 g, 950 mmoles) is added dropwise to the mechanically stirred mixture. The mixture is heated at reflux for 3 hours and allowed to stand at room temperature overnight. The suspension is cooled (<5°), 10% ammonium chloride solution is added and the mixture is extracted with ether. The combined extracts are dried (MgSO4) and evaporated. The residue is crystallized from hexane to give the title compound, mp 86°-90° C.
Reaction SMILES: [CH3:1][SiH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:11]=[CH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:1][Si:2]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C=CCCCCCCCC
Reactant: CCCCCCCC[SiH2]C
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCCCC[Si](C)(CCCCCCCC)CCCCCCCCCC
Yield: 86 %

Procedure:
A mixture of 72.6 grams methyloctylsilane and 200 grams of 1-decene was reacted in the presence of 0.0042 gram of chlorotris(triphenylphosphine)rhodium(I) for one hour at 87°-100° C. After stripping off unreacted decene under high vacuum, followed by hydrogenation of the residue, and distillation, resulted in an 86 percent yield of methyldidecyloctylsilane having a boiling point of 200°-206° C. (0.25 mm).
Reaction SMILES: [ClH:1].[CH3:2][O:3][C:4](=[O:18])[C@H:5]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:17])[CH:15]=2)[NH:10][CH:9]=1)[NH2:6].C=O.[CH3:21]COCC>CO>[ClH:1].[F:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]1[CH2:21][NH:6][C@H:5]([C:4]([O:3][CH3:2])=[O:18])[CH2:7][C:8]2=1
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccc(F)cc12
Reactant: CCOCC
Agent: C=O
Agent: Cl
Solvent: CO
Product: COC(=O)[C@@H]1Cc2c([nH]c3ccc(F)cc23)CN1
Temperature: 25 °C
Reaction time: 20 h
Yield: 68 %

Procedure:
0.93 g of 5-fluoro-L-tryptophan methyl ester hydrochloride is dissolved in 14 ml of methanol. 0.52 g of 35% formalin is added thereto and the mixture is stirred at room temperature for 20 hours. Ether is added to the mixture and crystalline precipitates are collected by filtration, washed with ether and dried, whereby 0.66 g of methyl (3S)-6-fluoro-1,2,3,4-tetrahydro-β-carboline-3-carboxylate hydrochloride are obtained as colorless needles. Yield: 68%
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11](O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C.C1(P([N:64]=[N+:65]=[N-:66])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCCC1.C(OCC)C>[N:64]([C@@H:11]1[CH2:12][CH2:13][C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[N+:65]=[N-:66]
Reactant: O[C@H]1CC[C@H](c2ccc(Br)cc2)CC1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: [N-]=[N+]=N[C@H]1CC[C@@H](c2ccc(Br)cc2)CC1
Temperature: -5 °C
Reaction time: 0.08 h

Procedure:
(trans)-4-(4-Bromophenyl)cyclohexanol (500 mg) is dissolved under argon in tetrahydrofurane (8 mL) and cooled to −5° C. Triphenylphosphine (770 mg) and di-tert-butyl-azodicarboxylate (550 mg) are added and the mixture is stirred for 5 minutes. A solution of diphenylphosphorylazide (650 μL) in tetrahydrofurane (8 mL) is added dropwise during 2 hours and the mixture is stirred at 0° C. for 48 hours. Then the mixture is diluted with diethylether, washed with saturated aqueous NaHCO3 solution and the organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (petrole ether/ethyl acetate 99:1→70:30) to give the title compound. LC (method 4): tR=0.97 min.
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][OH:17])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[C-:20]#[C-:21].[Na+].[Na+]>C#C>[F:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][OH:17])=[CH:10][CH:9]=2)([OH:7])[C:20]#[CH:21])=[CH:4][CH:3]=1
Reactant: [C-]#[C-]
Reactant: O=C(c1ccc(F)cc1)c1ccc(OCCO)cc1
Agent: C#C
Agent: [Na+]
Product: C#CC(O)(c1ccc(F)cc1)c1ccc(OCCO)cc1
Temperature: 25 °C

Procedure:
A photochromic group initiator (represented by structure 1.3 in Table 1 above) was prepared as follows. Step 1: 4-fluoro-4′-(2-hydroxyethoxy)-benzophenone from Part A, Step 1 of Example 7 (below) (7-974) (43.3 grams) and acetylene saturated N,N-dimethylformamide (130 mL) were combined in a reaction flask. Reaction flask was cooled in an ice bath. Sodium acetylide solution (9% by weight in toluene, 221 grams) was added to the cooled reaction mixture dropwise over 30 minutes. The ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was poured into ice water (450 mL) and diethyl ether (300 mL) was added to it. The layers were phase separated and the aqueous layer was extracted one time with diethyl ether (300 mL) and twice with ethyl acetate (300 mL each). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The resulting residue was purified by column chromatography on silica gel (600 grams) eluting with a mixture of 45% ethyl acetate in hexanes. The fractions containing pure desired product were combined and concentrated by rotary evaporation to yield 30.1 grams of 1-(4-fluorophenyl)-1-(4′-(2-hydroxyethoxy)phenyl)-2-propyn-1-ol.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH3:6].[PH2:7](=[O:9])[OH:8]>>[CH2:1]([PH:7](=[O:8])[OH:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=[PH2]O
Reactant: C=CCCCC
Product: CCCCCC[PH](=O)O

Procedure:
The title compound was prepared from n-hexene and 50% aqueous phosphinic acid by an analogous procedure to that described in J. Inorg. Nucl. Chem., 1965, 27, 697.
Reaction SMILES: O.C(=O)([O-])[O-].[Na+].[Na+].[C:8]([C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)([CH3:11])([CH3:10])[CH3:9].Br[C:22]1[S:23][C:24](Br)=[CH:25][C:26]=1[Br:27]>O.C1COCC1.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>[Br:27][C:26]1[CH:25]=[C:24]([C:15]2[CH:16]=[CH:17][C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:13][CH:14]=2)[S:23][C:22]=1[C:15]1[CH:16]=[CH:17][C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:13][CH:14]=1
Reactant: Brc1cc(Br)c(Br)s1
Reactant: CC(C)(C)c1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)c1ccc(-c2cc(Br)c(-c3ccc(C(C)(C)C)cc3)s2)cc1
Yield: 88.3 %

Procedure:
Sodium carbonate monohydrate (58.0 g, 468 mmol) was dissolved in water (500 mL) and a solution of 4-(tert-butyl)-phenylboronic acid (40.0 g) and 2,3,5-tribromothiophene (30.0 g, 94 mmol) in THF (500 mL) was added, and deoxygenated by bubbling with argon. Pd(PPh3)4 (5.0 g, 4.30 mmol) was added and the mixture refluxed for 24 h. The mixture was cooled and the aqueous phase separated and extracted with EtOAc. Organic fractions were combined washed with water (500 mL) and dried over MgSO4. The solvent was evaporated and the crude product washed in MeOH, filtered and dried overnight to afford a light yellow, powdery solid (35.46 g, 89%).
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:22]=[CH:21][C:9]([O:10][Si](C(C)C)(C(C)C)C(C)C)=[C:8]([F:23])[CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCCCCCC.C(OCC)(=O)C>C1COCC1.ClCCl>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:22]=[CH:21][C:9]([OH:10])=[C:8]([F:23])[CH:7]=1
Reactant: CC(C)[Si](Oc1ccc(C2OCCO2)cc1F)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: Oc1ccc(C2OCCO2)cc1F
Yield: 52 %

Procedure:
To a solution of (4-[1,3]dioxolan-2-yl-2-fluorophenoxy)triisopropylsilane (Example 93. Part B) (105.9 g, approximately 0.311 mol) in THF (1.589 L) add 1.0 M tetrabutylammonium fluoride (TBAF) in THF (311 mL) in a steady stream over 5 min at 23-27° C. without cooling. Stir for 1 hr till the reaction complete by TLC (19:1 heptane/ethyl acetate). Concentrate to a red oil and partition between ether (500 mL) and deionized water (1 L). Separate the layers and extract the aqueous layer with ether (500 mL). Combine the ether layers, wash with brine and dry over sodium sulfate. Filter and concentrate to give the crude product (92.9 g. Dissolve the crude product in dichloromethane and filter through 400 g of silica gel 60. Wash with dichloromethane (3×1 L fractions) and concentrate the combined filtrate to give an impure product. Crystallize from dichloromethane/heptane to give the title compound (29.8 g, 52%). Gas chromatography: retention time 15.96 min (30 m×0.32 mm i.d. DB-1 column, 0.25 micron film thickness; 1.2 mL/min flow rate; 55:1 split ratio; temperature profile: 35° C./3 min, 10° C. temperature increase per min; 250° C./10.5 min). 1H NMR (DMSO-d6) δ 3.84-3.93 (m, 2H, CH2), 3.93-4.04 (m, 2H, CH2), 5.60 (s, 1H, CH), 6.91 (t, 11, ArH), 7.06 (dd, 1H, ArH), 7.15 (dd, 1H, ArH), 10.0 (s, 1H, OH).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH2:16][CH2:15]2)=[O:13])=[CH:5][CH:4]=1)#[N:2].Cl.C.[H][H].[K+].[Br-]>CO.[Pd]>[NH2:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH2:16][CH2:15]2)=[O:13])=[CH:7][CH:8]=1
Reactant: [H][H]
Reactant: N#Cc1ccc(C(=O)CCC(=O)N2CCC(N3Cc4ccccc4NC3=O)CC2)cc1
Agent: [Pd]
Agent: Cl
Agent: [Br-]
Solvent: CO
Product: NCc1ccc(CCCC(=O)N2CCC(N3Cc4ccccc4NC3=O)CC2)cc1

Procedure:
A solution of 0.48 g (1.153 mmol) of 3-{1-[4-(4-cyanophenyl)-1,4-dioxobutyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone (Item no. 73) and 1.15 ml of 1N hydrochloric acid in 100 ml of methanol was hydrogenated at ambient temperature under 3 bar of pressure in the presence of 0.25 g of 10% palladium on active charcoal until the uptake of hydrogen had ended. The mixture was freed from catalyst and solvent and yielded 0.27 g (58% of theoretical) of a colourless substance, Rf 0.30 (El A). IR (KBr): 1662.5 (C═O) MS: M+406; ESI: (M+H)+=407
Reaction SMILES: Br[CH2:2][C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]#[N:11])=[O:4].[NH2:12][CH:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][CH:17]1[C:21]([NH2:23])=[O:22])=[O:15]>C1COCC1>[C:10]([C@@H:6]1[CH2:7][CH2:8][CH2:9][N:5]1[C:3](=[O:4])[CH2:2][NH:12][C@@H:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]([NH2:23])=[O:22])=[O:15])#[N:11]
Reactant: CC(C)CC(N)C(=O)N1CCCC1C(N)=O
Reactant: N#C[C@@H]1CCCN1C(=O)CBr
Solvent: C1CCOC1
Product: CC(C)C[C@H](NCC(=O)N1CCC[C@H]1C#N)C(=O)N1CCC[C@H]1C(N)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.3 %

Procedure:
A solution of 1-(2-bromo-acetyl)-(S)-pyrrolidine-2-carbonitrile (44 mg, 0.2 mmol) in THF (1 mL) was added slowly to a cold solution (−15° C.) of 1-(2-amino-4-methyl-pentanoyl)-pyrrolidine-2-carboxylic acid amide (55 mg, 0.24 mmol) in THF (2 mL). The temperature of the reaction mixture was gradually increased to room temperature. After stirring at this temperature overnight, the residue was concentrated and purified by LCMS to yield 1{(S)-2-[2-(2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amide (54 mg; 62%). This pure product (20 mg) was dissolved in THF (1 mL), HCl ether (0.1 mL; 2M) was added and the mixture was concentrated to give the HCl salt form of 1-{(S)-2-[2-(2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-(S)-4-methyl-pentanoyl}-(S)-pyrrolidine-2-carboxylic acid amide. 1H-NMR data (CDCl3—CD3OD, 20:1): δ, 8.25 and 6.25 (s, 1H each), 4.73 (m, 1H), 4.43 (t, 1H, J=5.4 Hz), 4.2 (d, 1H, J=14.1 Hz), 4.0-3.47 (m, 7H), 2.4-1.9 (m, 10H), 1.41 (m, 1H). MS: calculated for C18H29N5O3+H 364.2; found: 364.2.