Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]1[S:11][C:10]2[C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:8][C:7]([Cl:18])=[N:6][C:5]=2[CH:4]=1.[P:19](OC)([O:23][CH3:24])([O:21][CH3:22])=[O:20]>O>[CH3:22][O:21][P:19]([CH2:2][C:3]1[S:11][C:10]2[C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:8][C:7]([Cl:18])=[N:6][C:5]=2[CH:4]=1)(=[O:20])[O:23][CH3:24]
Reactant: COP(=O)(OC)OC
Reactant: Clc1nc(N2CCOCC2)c2sc(CBr)cc2n1
Solvent: O
Product: COP(=O)(Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1)OC
Temperature: 25 °C

Procedure:
A mixture of 6-bromomethyl-2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine 30 from Example 9 (1.0 g) and trimethyl phosphate (5 mL) was heated at reflux for 3 h. After cooling to room temperature, water (20 mL) was added and the product filtered, washed with water and dried under vacuum to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-phosphonic acid dimethyl ester as a yellow solid (0.54 g).
Reaction SMILES: [C:1]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.O[C:16]1C=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:17]=1C=O>N1CCCCC1>[C:1]([C:9]1[C:10](=[O:11])[O:12][C:13]2[C:17]([CH:16]=1)=[CH:20][CH:21]=[C:22]([O:24][CH3:25])[CH:14]=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: CCOC(=O)CC(=O)c1cccnc1
Reactant: COc1ccc(C=O)c(O)c1
Solvent: C1CCNCC1
Product: COc1ccc2cc(C(=O)c3cccnc3)c(=O)oc2c1

Procedure:
A mixture of 0.65 g ethyl nicotinoylacetate, 0.5 g 2-hydroxyanisaldehyde and 10 ml alcohol was heated on a steam bath until solution was attained. Five drops of piperdine were added and heating was continued. After several minutes the reaction mixture solidified. An additional 10 ml of alcohol were added and the reaction mixture heated another 15 minutes. After cooling, the solid was collected and recrystallized twice from a mixture of alcohol and acetonitrile.
Reaction SMILES: [NH:1]1[C:5]([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH2:14][OH:15])[CH:9]=[CH:10][CH:11]=2)=[N:4][N:3]=[N:2]1.C(N(CC)CC)C.[C:23]1([C:29]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)Cl)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>ClCCl>[C:23]1([C:29]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[N:3]2[N:2]=[N:1][C:5]([C:6]3[CH:7]=[C:8]([CH:12]=[CH:13][CH2:14][OH:15])[CH:9]=[CH:10][CH:11]=3)=[N:4]2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: OCC=Cc1cccc(-c2nnn[nH]2)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: OCC=Cc1cccc(-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of 3-[3-(1H-tetrazol-5-yl)phenyl]-2-propenol (2.02 g) in dry dichloromethane (50 ml) was added triethylamine (1.5 ml) followed by triphenylchloromethane (2.8 g) in dry dichlormethane. The solution was stirred at room temperature for 90 minutes, washed with water (50 ml), followed by sodium bicarbonate solution (5%; 50 ml), dried over magnesium sulphate, filtered and evaporated under reduced pressure to give a pale brown viscous oil which crystallised on standing to a cream solid.
Reaction SMILES: [ClH:1].Cl.C[O:4][C:5](=[O:15])[C@H:6]([CH2:8][N:9]1[CH:13]=[CH:12][N:11]=[C:10]1[NH2:14])[NH2:7]>Cl>[ClH:1].[ClH:1].[NH2:14][C:10]1[N:9]([CH2:8][C@@H:6]([C:5]([OH:15])=[O:4])[NH2:7])[CH:13]=[CH:12][N:11]=1
Reactant: COC(=O)[C@@H](N)Cn1ccnc1N
Agent: Cl
Product: Nc1nccn1C[C@H](N)C(=O)O
Temperature: 55 °C
Reaction time: 120 h
Yield: 117.1 %

Procedure:
3-(2-Aminoimidazol-1-yl)-L-alanine methyl ester dihydrochloride (103 mg) was dissolved in 6N hydrochloric acid (4 ml), and the mixture was stirred at 55° C. for 5 days. The solvent was evaporated under reduced pressure. Methanol was added to the residue, and the insoluble materials were filtered off. Evaporation of the solvent in the filtrate gave the title compound (57 mg).
Reaction SMILES: [CH3:1][Se:2][C:3]1[C:4]([NH2:48])=[N:5][C:6](=[O:47])[N:7]([CH:46]=1)[C@@H:8]1[O:38][C@H:12]([CH2:13][O:14][C:15]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:16]2[CH:21]=[CH:20][C:19]([O:24][CH3:25])([O:22][CH3:23])[CH2:18][CH:17]=2)[C@@:10]([Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])([OH:11])[CH2:9]1.[C:49](Cl)(=[O:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C(OCC)(=O)C>CCCCCC>[C:49]([NH:48][C:4]1[C:3]([Se:2][CH3:1])=[CH:46][N:7]([C@@H:8]2[O:38][C@H:12]([CH2:13][O:14][C:15]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])([O:24][CH3:25])[CH2:20][CH:21]=3)[C@@:10]([Si:39]([C:42]([CH3:43])([CH3:44])[CH3:45])([CH3:40])[CH3:41])([OH:11])[CH2:9]2)[C:6](=[O:47])[N:5]=1)(=[O:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1
Reactant: COC1(OC)C=CC(C(OC[C@H]2O[C@@H](n3cc([Se]C)c(N)nc3=O)C[C@@]2(O)[Si](C)(C)C(C)(C)C)(c2ccccc2)c2ccccc2)=CC1
Reactant: O=C(Cl)c1ccccc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COC1(OC)C=CC(C(OC[C@H]2O[C@@H](n3cc([Se]C)c(NC(=O)c4ccccc4)nc3=O)C[C@@]2(O)[Si](C)(C)C(C)(C)C)(c2ccccc2)c2ccccc2)=CC1
Reaction time: 1 h

Procedure:
5-methylseleno-3′-t-butyldimethylsilyl-5′-O-(4,4-dimethoxytrityl)-2′-deoxycytidine (compound 2) 300 mg (MW 751.3, 0.4 mmol) was placed in a flask and dried on high vacuum for one hour before addition of anhydrous pyridine 10 ml. Benzoyl chloride 0.03 ml (0.6 mmol, 1.5 eq.) was added dropwise before the reaction solution was stirred for 1 hour. After the reaction was completed (monitored on TLC, 30% ethyl acetate in hexane, Rf=0.5), the crude product was extracted with saturated NaCl solution and ethyl acetate. The organic phase was removed and aqueous phase was extracted with ethyl acetate three times. The combined organic phase was dried over anhydrous MgSO4, the salt was filtered, and the organic solvents were evaporated under reduced pressure. The residue was purified on a silica gel column (equilibrated with hexane) and eluted with an ethyl acetate/hexane gradient (EtOAc in hexane, 10-50%). Compound 3 was isolated and dried to afford a yellow-green solid 287 mg. (yield=84%). 1H-NMR (400 MHz, DMSO) δ: 0.09 and 0.04 [2×s, 6H, Si(CH3)2], 0.86 (s, 9H, t-butyl), 2.02 (s, 3H, SeCH3), 2.18-2.20 and 2.43-2.52 (2×m, 2H, H-2′), 3.29-3.33 and 3.43-3.46 (2×m, 2H, H-5′), 3.81 (s, 6H, 2×OMe), 4.05-4.08 (m, 1H, H-3′), 4.41-4.45 (m, 1H, H-4′), 6.30-6.34 (t, J=6.4 Hz, 1H, H-1′), 6.86-7.56 (m, 18H, arom-H), 7.88 (s, 1H, NH), 8.32 (s, 1H, H-6). 13C NMR (100 MHz, DMSO) δ: −4.89 and −4.69 [Si(CH3)2], 1.03 (SeCH3), 17.95 [SiC(CH3)], 25.73 [SiC(CH3)], 41.86 (C-2′), 55.26 (OMe), 63.05 (C-5′), 72.41 (C-3′), 86.30 (C-4′), 86.77 (C-5), 87.24 (C-1′), 113.27 (arom-C), 127.07 (arom-C), 128.13 (arom-C), 128.27 (arom-C), 129.38 (arom-C), 130.09 (arom-C), 132.67 (arom-C), 133.68 (C-6), 135.51 (NHCO), 144.41 (arom-C), 144.36 (C-2), 158.69 (C-4). HR-MS (ESI-TOF, negative ion mode): molecular formula, C44H51N3O7SeSi: [M−H]−: 840.2570 (calc. 840.2583)
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:14]=[CH:13][NH:12][N:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O[C@H:16]([CH3:26])[CH2:17][NH:18]C(=O)OC(C)(C)C>>[NH2:18][CH2:17][C@H:16]([N:12]1[CH:13]=[CH:14][C:10]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[CH:9]=2)=[N:11]1)[CH3:26]
Reactant: C[C@@H](O)CNC(=O)OC(C)(C)C
Reactant: N#Cc1ccc(-c2cc[nH]n2)cc1Cl
Product: C[C@H](CN)n1ccc(-c2ccc(C#N)c(Cl)c2)n1

Procedure:
(R)-4-[1-(1-Aminopropan-2-yl)-1H-pyrazol-3-yl]-2-chlorobenzonitrile was prepared using the method of Example 34(c) starting from 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile and (R)-tert-butyl 2-hydroxypropylcarbamate. 1H NMR (400 MHz, CDCl3): 1.24 (21-1, broad s), 1.54 (3H, d), 3.05 (1H, distorted dd), 3.17 (1H, distorted dd), 4.34 (1H, m), 6.61 (1H, d), 7.52 (1H, d), 7.66 (1H, d), 7.78 (1H, dd), 7.98 (1H, d).
Reaction SMILES: Cl.Cl.[CH3:3][C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:5]=1[CH2:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.ClCCl.[O:35]1[CH:39]=[CH:38][CH:37]=[C:36]1[C:40](Cl)=[O:41]>C(N(CC)CC)C>[CH3:3][C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:5]=1[CH2:25][N:26]1[CH2:31][CH2:30][N:29]([C:40]([C:36]2[O:35][CH:39]=[CH:38][CH:37]=2)=[O:41])[CH2:28][CH2:27]1
Reactant: Cc1nc(-c2ccccc2)nc(-c2cccc([N+](=O)[O-])c2)c1CN1CCNCC1
Reactant: O=C(Cl)c1ccco1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(-c2ccccc2)nc(-c2cccc([N+](=O)[O-])c2)c1CN1CCN(C(=O)c2ccco2)CC1
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a mixture of 6-methyl-5-(1-piperazinylmethyl)-4-(3-nitrophenyl)-2-phenylpyrimidine dihydrochloride (1 g), dichloromethane (10 ml) and triethylamine (0.48 g), was added 2-furoyl chloride (0.31 g) at 5° C. under ice cooling. After stirring for 1 hour at the same temperature, the reaction mixture was concentrated under reduced pressure. The residue was suspended in water and adjusted to pH=9 with aqueous saturated sodium hydrogen carbonate. The precipitate was collected by filtration, washed with water and dried in vacuo to give 6-methyl-5-[4-(2-furoyl)piperazin-1-ylmethyl]-4-(3-nitrophenyl)-2-phenylpyrimidine (1.02 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:18])[NH:16][CH:17]=2)=[O:11])=[CH:4][CH:3]=1.IC.[C:26](=O)([O-])[O-].[K+].[K+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:18])[N:16]([CH3:26])[CH:17]=2)=[O:11])=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(CC(c1ccc(Br)cc1)C1CCCC1)c1ccc(=O)[nH]c1
Agent: [K+]
Solvent: CI
Product: Cn1cc(C(=O)CC(c2ccc(Br)cc2)C2CCCC2)ccc1=O

Procedure:
In analogy to example 161, step 1, 5-[3-(4-bromo-phenyl)-3-cyclopentyl-propionyl]-1H-pyridin-2-one was reacted with iodomethane in the presence of potassium carbonate to give the title compound as a colorless foam, MS (ESI+): m/z=388.2 [M+H]+.
Reaction SMILES: C([O:4][C@H:5]([CH3:29])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:19](=[O:20])[C:18]2[N:17]([CH3:21])[CH:16]=[N:15][C:14]=2[N:13]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]#[N:28])[C:11]1=[O:12])(=O)C.Cl.O1CCOCC1>CO>[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][N:13]1[C:14]2[N:15]=[CH:16][N:17]([CH3:21])[C:18]=2[C:19](=[O:20])[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]([OH:4])[CH3:29])[C:11]1=[O:12])#[N:28]
Reactant: CC(=O)O[C@H](C)CCCCn1c(=O)c2c(ncn2C)n(CCCCCC#N)c1=O
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: C[C@@H](O)CCCCn1c(=O)c2c(ncn2C)n(CCCCCC#N)c1=O
Temperature: 80 °C
Yield: 45.1 %

Procedure:
To a stirring solution of 0.37 g (R)-1-(5-acetoxyhexyl)-3-(5-cyanopentyl)-7-methylxanthine (0.92 mmol) in 20 ml methanol was added a solution of 4M hydrogen chloride in 70 ml 1,4-dioxane (2.77 mmol). The reaction was heated at reflux (80° C.) for five hours and then cooled to room temperature. The solvent was removed under reduced pressure and the resulting oil was treated with 25 ml saturated aqueous sodium bicarbonate solution and extracted three times with 25 ml dichloromethane. The combined extracts were washed 2× with 25 ml saturated aqueous sodium chloride solution dried over sodium sulfate, and concentrated under vacuum. The resulting residue was purified by flash chromatography eluting with 10% methanol-ethyl acetate to give 0.15 g (R)-3-(5-cyanopentyl)-1-(5-hydroxyhexyl)-7-methylxanthine (47% yield) as a viscous oil.
Reaction SMILES: Br[C:2]1[N:7]2[N:8]=[C:9]([NH2:11])[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[C:12]([O:15][CH2:16][CH3:17])(=O)C>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].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>[CH3:12][O:15][C:16]1[CH:17]=[CH:5][C:4]([C:2]2[N:7]3[N:8]=[C:9]([NH2:11])[N:10]=[C:6]3[CH:5]=[CH:4][CH:3]=2)=[CH:3][CH:2]=1
Reactant: CCOC(C)=O
Reactant: Nc1nc2cccc(Br)n2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COc1ccc(-c2cccc3nc(N)nn23)cc1
Yield: 83 %

Procedure:
A solution of 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine (1.5 g, 7.0 mmol, 1 equiv) and bis(triphenylphosphine)palladium(II) chloride (500 mg, 0.7 mmol 0.1 equiv) in acetonitrile (10 mL) and 1M aqueous sodium carbonate solution (10 mL) was heated at 120° C. for 3 min in the microwave. The reaction mixture was diluted with ethyl acetate, and the resulting solution was washed water (2×) and saturated aqueous sodium chloride solution. Purification by flash column chromatography (2→10% methanol in dichloromethane) provided product (1.4 g, 83%). 1H NMR (400 MHz, CDCl3), δ: 7.90 (d, 2H), 7.48 (m, 1H), 7.39 (m, 1H), 7.05 (d, 2H), 6.88 (dd, 1H), 4.25 (s, 2H); ES-MS m/z 241.0.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:22][CH3:23])=[C:18]([OH:21])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[CH:2].Cl[CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][CH:31]2[CH2:34][O:35][CH2:36][CH:30]2[CH2:29]1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:22][CH3:23])=[C:18]([O:21][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][CH:31]5[CH2:34][O:35][CH2:36][CH:30]5[CH2:29]4)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[CH:2]
Reactant: C#Cc1cc(Nc2ncnc3cc(OC)c(O)cc23)ccc1F
Reactant: ClCCCN1CCC2COCC2C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C#Cc1cc(Nc2ncnc3cc(OC)c(OCCCN4CCC5COCC5C4)cc23)ccc1F
Temperature: 80 °C
Reaction time: 8 h
Yield: 52.5 %

Procedure:
A mixture of 4-((3-ethynyl-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (220 mg, 0.71 mmol, 1 eq), 5-(3-chloropropyl)octahydrofuro[3,4-c]pyridine (174 mg, 0.44 mmol, 1.2 eq) and K2CO3 (197 mg, 1.42 mmol, 2 eq) in DMF (10 mL) was stirred at 80° C. overnight, and cooled to room temperature. To this, CH2Cl2 (50 mL) was added. The mixture was washed with brine (20 mL×3) and water (20 mL×2), then dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by a silica gel column chromatography (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound as a yellow solid (110 mg, 32.50%), HPLC: 97.45%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 477.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.76-1.77 (2H, m), 2.24-2.48 (3H, m), 2.50-2.64 (2H, m), 2.68-2.71 (3H, m), 2.73-2.75 (2H, m), 2.96-3.03 (3H, m), 3.07-3.12 (2H, m), 3.61-3.90 (2H, m), 4.07 (1H, s), 4.24-4.27 (2H, m), 7.06-7.10 (1H, m), 7.16 (1H, s), 7.76-7.82 (1H, m), 7.82 (1H, s), 8.09-8.11 (1H, m), 8.59 (1H, s) ppm.
Reaction SMILES: [I-].[CH3:2][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Si:22]([O:29][CH2:30][CH2:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>C1COCC1>[C:25]([Si:22]([CH3:24])([CH3:23])[O:29][CH2:30][CH2:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[CH2:2])=[CH:35][CH:34]=1)([CH3:28])([CH3:27])[CH3:26]
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)[Si](C)(C)OCCOc1ccc(C=O)cc1
Agent: [I-]
Solvent: C1CCOC1
Product: C=Cc1ccc(OCCO[Si](C)(C)C(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 65.6 %

Procedure:
To a cold suspension of methyl triphenyl phosphonium iodide (2.88 g, 7.13 mmol) in THF (20 mL) was added KOBt (0.88 g, 7.84 mmol) slowly. The reaction mixture was warmed to RT and stirred for about 1 h. A solution of 4-(2-(tert-butyldimethylsilyloxy)ethoxy)benzaldehyde (1.0 g, 3.56 mmol) in THF (15 mL) was added slowly to the above reaction mixture and stirred for about another 3 h. The reaction was quenched with water and extracted with diethyl ether (3×75 mL). The combined organic extracts were washed with brine (1×75 mL), dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography using 10% EtOAc-hexane as the eluent. Relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford tert-buyldimethyl (2-(4-vinylphenoxy)ethoxy)silane 0.65 g, (65%), 1H NMR (400 MHz, CDCl3): δ 7.350-7.342 (d, J=3.2 Hz, 2H), 6.882-6.875 (d, J=2.8 Hz, 2H), 6.857-6.692 (m, 1H), 5.625-5.581 (d, J=17.6 Hz, 1H), 5.132-5.104 (d, J=11.2 Hz, 1H), 4.052-3.954 (m, 4H), 0.909 (s, 9H), 0.1 (s, 6H), MS m/z: 279.3 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:19])[CH:15]([CH3:18])[CH:16]=[CH2:17])=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23]([C:25]1([C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)[CH2:27][CH2:26]1)=[O:24])[CH3:21]>>[CH2:20]([O:22][C:23]([C:25]1([C:28]2[CH:33]=[CH:32][C:31]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH:14]([OH:19])[CH:15]([CH3:18])[CH:16]=[CH2:17])=[CH:4][CH:3]=3)=[CH:30][CH:29]=2)[CH2:26][CH2:27]1)=[O:24])[CH3:21]
Reactant: C=CC(C)C(O)c1c(C)noc1-c1ccc(Br)cc1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: C=CC(C)C(O)c1c(C)noc1-c1ccc(-c2ccc(C3(C(=O)OCC)CC3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 110, Step 3, using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-2-methyl-but-3-en-1-ol and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[CH:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:8][CH2:7]2.C1COCC1.[Li]CCCC.[Li]C(C)(C)C.C(O[B:37]1[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]1)(C)C>CCCCC>[C:12]1([NH:11][CH:9]2[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[B:37]3[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]3)[CH2:7][CH2:8]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Brc1cccc2c1C(Nc1ccccc1)CC2
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Agent: [Li]C(C)(C)C
Agent: [Li]CCCC
Solvent: CCCCC
Solvent: C1CCOC1
Product: CC1(C)OB(c2cccc3c2C(Nc2ccccc2)CC3)OC1(C)C
Reaction time: 1 h

Procedure:
To a solution of 2.50 g (8.70 mmol) of 7-bromo-N-phenyl-2,3-dihydro-1H-inden-1-amine in 50 ml THF 3.50 ml (8.70 mmol) of 2.5M nBuLi in hexanes was added at −80° C. in argon atmosphere. The reaction mixture was then stirred for 1 h at this temperature. Further on, 11.1 ml (17.8 mmol) of 1.7M tBuLi in pentane was added, and the reaction mixture was stirred for 1 h. Then, 3.23 g (17.4 mmol) of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was added. After that the cooling bath was removed, and the resulting mixture was stirred for 1 h at room temperature. To the formed mixture 10 ml of water was added, and the resulting mixture was evaporated to dryness. The residue was diluted with 200 ml of water, and the title product was extracted with 3×50 ml of ethyl acetate. The combined organic extract was dried over Na2SO4 and evaporated to dryness. Yield 2.80 g (96%) of a light yellow oil. Anal. calc. For C21H26BNO2: C, 75.24; H, 7.82; N, 4.18. Found: C, 75.40; H, 8.09; N, 4.02. 1H NMR (CDCl3): δ 7.63 (m, 1H, 6-H in indane); 7.37-7.38 (m, 1H, 4-H in indane); 7.27-7.30 (m, 1H, 5-H in indane); 7.18 (m, 2H, 3,5-H in phenyl); 6.65-6.74 (m, 3H, 2,4,6-H in phenyl); 5.20-5.21 (m, 1H, 1-H in indane); 3.09-3.17 (m, 1H, 3- or 3′-H in indane); 2.85-2.92 (m, 1H, 3′- or 3-H in indane); 2.28-2.37 (m, 1H, 2- or 2′-H in indane); 2.13-2.19 (m, 1H, 2′- or 2-H in indane); 1.20 (s, 6-H, 4,5-Me in BPin); 1.12 (s, 6H, 4′,5′-Me in BPin).
Reaction SMILES: [C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].Br[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[N:17][CH:18]=1.C(N(CC)CC)C>CN(C)C=O.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[Pd]Cl.[Cu]I>[CH2:20]([O:19][C:16]1[N:17]=[CH:18][C:13]([C:2]#[C:1][C:3]2([OH:11])[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)=[CH:14][CH:15]=1)[CH2:21][CH2:22][CH3:23]
Reactant: C#CC1(O)CN2CCC1CC2
Reactant: CCCCOc1ccc(Br)cn1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCOc1ccc(C#CC2(O)CN3CCC2CC3)cn1
Temperature: 90 °C
Yield: 25.2 %

Procedure:
A stirred mixture of 3-ethynyl-3-hydroxyquinuclidine (600 mg), 5-bromo-2-n-butoxypyridine (920 mg), bis-(triphenylphosphine)-palladium (II) chloride (140 mg), copper (I) iodide (70 mg) and dry triethylamine (10 ml) in dry dimethylformamide (20 ml) was heated at 90° C. under an atmosphere of argon for 6 hours. The reaction mixture was cooled and the dimethylformamide and triethylamine were removed by evaporation. The residue was treated with 2M aqueous sodium hydroxide solution (20 ml) and the resulting mixture extracted with dichloromethane (3×20 ml). The organic extracts were combined, dried (MgSO4) and evaporated to give a brown residue which was crystallised from acetonitrile to yield 3-[2-(6-butoxy-3-pyridyl)ethynyl]quinuclidin-3-ol (300 mg) as a solid, m.p. 149°-151° C.; microanalysis, found: C, 71.3; H, 7.9; N, 8.9%; C18H24N2O2 0.1H 2O requires: C, 71.47; H, 8.08; N, 9.26%; NMR (DHSOd6): 0.9-1.0(3H, t), 1.2-1.35(1H, m), 1.35-1.5(2H, m), 1.5-1.65(1H, m), 1.65-1.75(2H, m), 1.75-2.0(3H, m), 2.6-2.75(4H, t), 2.8-2.85(1H, d), 3.02-3.17(1H, d), 4.2-4.3(2H, t), 5.55(1H, s), 6.75-6.83(1H, d), 7.65-7.72(1H, d) and 8.2(1H, s); m/Z 301 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C:8]2[S:9][CH:10]=[C:11]([C:13]([O:15]CC)=[O:14])[N:12]=2)[CH:7]=1.[OH-].[Li+]>CO.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C:8]2[S:9][CH:10]=[C:11]([C:13]([OH:15])=[O:14])[N:12]=2)[CH:7]=1
Reactant: CCOC(=O)c1csc(-c2cc(Br)ccc2F)n1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1csc(-c2cc(Br)ccc2F)n1
Temperature: 50 °C
Reaction time: 2 h
Yield: 88.9 %

Procedure:
To a solution of ethyl 2-(5-bromo-2-fluoro-phenyl)thiazole-4-carboxylate (8.97 mmol, 2960 mg) in methanol (40 mL) and water (10 mL) was added lithium hydroxide (1.6 equiv., 14.2 mmol, 347 mg). The reaction mixture was stirred at 50° C. for 2 hours. The reaction mixture was cooled to room temperature, concentrated, suspended in water, and then quenched with 2N HCl(aq.). The solid was collected, washed with water, and dried under high vacuum to afford 2-(5-bromo-2-fluoro-phenyl)thiazole-4-carboxylic acid (2410 mg, 89% Yield) as a white solid.
Reaction SMILES: [C:1]1([CH:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH2:20])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:28]1[CH:29]=[CH:30][C:31]2[N:32]([N:34]=[CH:35][N:36]=2)[N:33]=1.C(=O)(O)[O-].[Na+]>>[C:1]1([CH:7]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:28]3[CH:29]=[CH:30][C:31]4[N:32]([N:34]=[CH:35][N:36]=4)[N:33]=3)[CH2:11][CH2:10]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Clc1ccc2ncnn2n1
Reactant: NCCCCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Product: c1ccc(C(OC2CCN(CCCCCNc3ccc4ncnn4n3)CC2)c2ccccc2)cc1
Yield: 66.9 %

Procedure:
0.705 g of 4-(diphenylmethoxy)-1-piperidinepentanamine and 0.309 g of 6-chloro[1,2,4]triazolo[1,5-b]pyridazine were stirred at 135-140° C. for 1.5 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; the extract was washed with saline and dried with sodium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (95:5:1). The desired fraction was collected, recrystallized from ethyl ether and dried to yield 0.629 g of the title compound.