Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([O:18][CH3:19])=[O:17])=[CH:15][C:10]=3[O:9][CH2:8][CH2:7][N:6]2[CH:20]=1)#[N:2].C(=O)([O-])[O-:22].[K+].[K+].OO>CS(C)=O.O>[C:1]([C:3]1[N:4]=[C:5]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([O:18][CH3:19])=[O:17])=[CH:15][C:10]=3[O:9][CH2:8][CH2:7][N:6]2[CH:20]=1)(=[O:22])[NH2:2]
Reactant: COC(=O)c1ccc2c(c1)OCCn1cc(C#N)nc1-2
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: COC(=O)c1ccc2c(c1)OCCn1cc(C(N)=O)nc1-2
Yield: 75.8 %

Procedure:
Methyl 2-cyano-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylate (0.46 g, 1.7 mmol) was stirred with potassium carbonate (469 mg, 3.4 mmol), water (1.2 mL) and hydrogen peroxide (408 mg, 6 mmol) in DMSO (7 mL) for 4 hours. The mixture was diluted with 70 mL of water and extracted with ethyl acetate. Ethyl acetate solution was washed with water, 5% Na2S2O3, water, brine, dried over MgSO4 and concentrated under vacuum to give methyl 2-carbamoyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylate (0.37 g)
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH2:21][CH2:22][N:23](C(OC(C)(C)C)=O)[CH2:24][CH:25]=3)=[CH:16][CH:15]=2)[CH2:12][C:11]([C:33]([C:39]([F:42])([F:41])[F:40])([C:35]([F:38])([F:37])[F:36])[OH:34])=[N:10]1.[F:43][C:44]([F:49])([F:48])[C:45]([O-:47])=[O:46]>ClCCl>[F:43][C:44]([F:49])([F:48])[C:45]([OH:47])=[O:46].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH:25]=3)=[CH:16][CH:15]=2)[CH2:12][C:11]([C:33]([C:39]([F:40])([F:41])[F:42])([C:35]([F:36])([F:37])[F:38])[OH:34])=[N:10]1
Reactant: O=C([O-])C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc(C3CC(C(O)(C(F)(F)F)C(F)(F)F)=NN3c3ccc(F)cc3F)cc2)CC1
Solvent: ClCCl
Product: O=C(O)C(F)(F)F
Product: OC(C1=NN(c2ccc(F)cc2F)C(c2ccc(C3=CCNCC3)cc2)C1)(C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.8 %

Procedure:
1-(2,4-Difluoro-phenyl)-5-[4-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (800.0 mg, 1.32 mmol) prepared in Example 398 and trifluoroacetate (1.0 mL, 13.05 mmol) were added at 0° C. to dichloromethane (6.0 mL). The reaction mixture was stirred at room temperature for 3 hours and then concentrated under reduced pressure to give 800.0 mg of the titled compound as a yellow liquid.
Reaction SMILES: [Br:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][CH:7]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:32][O:33][C:34](=[O:38])[CH2:35][CH2:36][NH2:37].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:32][O:33][C:34](=[O:38])[CH2:35][CH2:36][NH:37][C:18](=[O:20])[C:17]1[CH:16]=[CH:15][C:14]([CH:7]([O:6][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:24][CH:23]=2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:22][CH:21]=1
Reactant: CCCCCCC(Oc1ccc(Br)cc1)c1ccc(C(=O)O)cc1
Reactant: COC(=O)CCN
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCC(Oc1ccc(Br)cc1)c1ccc(C(=O)NCCC(=O)OC)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.1 %

Procedure:
To a mixture of 4-[1-(4-bromo-phenoxyl)-heptyl]-benzoic acid (1700 mg, 4.35 mmol) in methylene chloride (43 mL) are added triethyl amine (1.82 mL, 13.4 mmol), DMAP (5.0 mg), 3-amino-propionic acid methyl ester (910 mg, 6.52 mmol) and EDCI (2507 mg, 13.04 mmol) at room temperature. The reaction mixture is stirred at room temperature overnight, loaded on silica gel, eluted with eluted with hexanes with a gradient from 0% of ethyl acetate to 100% of ethyl acetate giving racemic 3-{4-[1-(4-bromo-phenoxyl)-heptyl]-benzoylamino}-propionic acid methyl ester (1660 mg).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[C:9]([OH:10])=[CH:8][CH:7]=[CH:6][N:5]2[C:11]=1[CH3:12].[CH2:13]([C:15]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:16]=1[CH2:17]Cl)[CH3:14].[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([O:10][CH2:17][C:16]3[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:15]=3[CH2:13][CH3:14])=[CH:8][CH:7]=[CH:6][N:5]2[C:11]=1[CH3:12]
Reactant: CCc1cccc(C)c1CCl
Reactant: Cc1nc2c(O)cccn2c1C
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: CCc1cccc(C)c1COc1cccn2c(C)c(C)nc12

Procedure:
2,3-Dimethyl-8-hydroxyimidazo[1,2-a]pyridine (0.8 g, 5 mmol), 2-ethyl-6-methylbenzyl chloride, sodium iodide (0.25 g, 1.7 mmol) and sodium carbonate (1.2 g, 11 mmol) were added to acetone (40 ml) and the mixture was refluxed for 5 h. The acetone was evaporated and the residue was solved in methylene chloride and washed with water. The organic solvent was dried and was evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using (a) methylene chloride: ethylacetate(1:2), (b) methylene chloride:ethylacetate(2:1), as eluent to give the title compound. (0.02 g, 1.4%)
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:12]([C:13](=[O:15])[N:14]=1)=[CH:11][C:10]([CH:16]([OH:18])[CH3:17])=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH3:4].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]2[N:37]([C:38]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:36]=[N:35][N:34]=2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([C:5]1[N:14]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[N:37]([C:38]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[N:36]=[N:35][N:34]=3)=[CH:25][CH:26]=2)[C:13](=[O:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:16]([OH:18])[CH3:17])[CH:11]=2)[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCCc1nc(=O)c2cc(C(C)O)ccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCc1nc2ccc(C(C)O)cc2c(=O)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Yield: 57.9 %

Procedure:
A suspension of 2.50 g of 2-butyl-6-(1-hydroxyethyl)-4(1H)-quinazolinone, 6.79 g of 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(triphenylmethyl)-1H-tetrazole and 4.20 g of anhydrous potassium carbonate in 225 ml of dry acetone is heated at reflux for 16 hours. The reaction mixture is allowed to cool to room temperature, filtered and the filtrate evaporated in vacuo. The residue is purified by high pressure liquid chromatography on silica gel by eluting with 1:2 ethyl acetate-hexanes to afford 4.25 g of the desired product as a white solid, FAB M+H 723.
Reaction SMILES: Cl[C:2]1[S:3][CH:4]=[C:5]([Cl:7])[N:6]=1.C(=O)([O-])[O-].[K+].[K+].[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>C(#N)C>[Cl:7][C:5]1[N:6]=[C:2]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[S:3][CH:4]=1
Reactant: Clc1csc(Cl)n1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Clc1csc(N2CCOCC2)n1
Temperature: 40 °C
Yield: 76.6 %

Procedure:
To a mixture of 2,4-dichlorothiazole (34 g, 0.22 mol) in acetonitrile (425 mL) add potassium carbonate (60.9 g, 0.44 mol) and then morpholine (21.2 mL, 0.225 mol) dropwise over 30 min. Reflux the mixture at 40° C. and then cool to 22° C. Filter the mixture and evaporate the filtrate. Triturate the residue with i-propyl alcohol (60 mL) at 22° C. for one hour. Filter the solids and dry under vacuum to a constant weight to afford the title compound (34.5 g, 76%). ES/MS m/z (35Cl) 205 (M+1)+.
Reaction SMILES: [N+:1]([C:4]1[C:5]([N:13]2[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14]2)=[C:6]2[S:12][CH:11]=[CH:10][C:7]2=[N:8][CH:9]=1)([O-])=O.[NH4+].[Cl-].CCO>[Fe].O>[NH2:1][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:14]2)=[C:6]2[S:12][CH:11]=[CH:10][C:7]2=[N:8][CH:9]=1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCN(c2c([N+](=O)[O-])cnc3ccsc23)C1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@H]1CCCN(c2c(N)cnc3ccsc23)C1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To a vial containing tert-butyl [(3S)-1-(6-nitrothieno[3,2-b]pyridin-7-yl)piperidin-3-yl]carbamate (210.1 mg, 0.5552 mmol), iron powder (306.1 mg, 5.481 mmol) and NH4Cl (491.9 mg, 9.196 mmol), EtOH (5.00 mL) was added, followed by water (1.00 mL). The mixture was stirred at 80° C. for 2 h. The reaction mixture was then filtered through a pad of diatomaceous earth. The diatomaceous earth pad was eluted with a 10% aq. K3PO4 (30 mL) and EtOAc (30 mL). The organic layer was washed with brine (30 mL), then dried over Na2SO4, and concentrated under reduced pressure. The resulting residue (197.9 mg) of the sub-title compound was used in the next step without further purification. LCMS calc. for C17H25N4O2S (M+H)+: m/z=349.2. found 349.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=3)=[C:11]([CH3:24])[O:10][N:9]=2)=[CH:4][CH:3]=1.Cl.[NH:26]1[CH2:31][CH2:30][S:29](=[O:33])(=[O:32])[CH2:28][CH2:27]1.C(N(CC)CC)C.O>C1COCC1.CN(C1C=CN=CC=1)C>[OH2:10].[O:32]=[S:29]1(=[O:33])[CH2:30][CH2:31][N:26]([C:19]([C:18]2[CH:17]=[N:16][C:15]([O:14][CH2:13][C:12]3[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:9][O:10][C:11]=3[CH3:24])=[CH:23][CH:22]=2)=[O:21])[CH2:27][CH2:28]1
Reactant: Cc1onc(-c2ccc(F)cc2)c1COc1ccc(C(=O)O)cn1
Reactant: O=S1(=O)CCNCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1onc(-c2ccc(F)cc2)c1COc1ccc(C(=O)N2CCS(=O)(=O)CC2)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid (23.0 g, 70.1 mmol) and 1,1-carbonyldiimidazole (15.3 g, 94.6 mol, 1.35 eq.) were dissolved in THF (120 mL) and the resulting solution was stirred for one hour at room temperature. This solution was then added to a suspension of thiomorpholine-1,1-dioxide HCl (16.9 g, 98.5 mmol), DMAP (400 mg, 3.27 mmol) and triethylamine (9.78 g, 96.7 mmol) in THF (120 mL). The resulting mixture was heated to reflux temperature and subsequently stirred at this temperature for 50 hours. The mixture was cooled to room temperature and then treated within one hour with water (300 mL). From the resulting suspension THF was distilled off under reduced pressure and with a jacket temperature of 60° C. and continuously replaced by ethanol (426 g) at constant volume. The suspension was cooled to room temperature and stirred for 2 hours. The crystals were filtered off, washed with a mixture of ethanol (100 mL) and water (100 mL) and subsequently dried at 55° C./<25 mbar until constant weight to afford 28.9 g (92%) of Form B as a colorless solid with purity of 99.7% (area) as measured by HPLC.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][NH:6][C:7](=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=1)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[Cl:1][CH2:2][C:3]1[O:16][C:7]([C:8]2[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=2)[C:14]#[N:15])=[N:6][N:5]=1
Reactant: N#Cc1cccc(C(=O)NNC(=O)CCl)c1
Agent: O=C([O-])[O-]
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Agent: [K+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: N#Cc1cccc(-c2nnc(CCl)o2)c1
Yield: 28.5 %

Procedure:
N′-(chloroacetyl)-3-cyanobenzohydrazide (795 mg, 3.34 mmol) and P2O5 (4.7 g, 33.4 mmol) were added to DMF (6 ml) and toluene (4 ml). The reaction mixture was refluxed for 2 h. K2CO3 (aq., sat.) was added until pH was basic and the mixture was extracted with DCM. The combined organic layers were dried (Na2SO4) and purified with flash chromatography using 0 to 100% EA in hep. to give the title compound (209 mg, 29%). 1H NMR: 8.29 (m, 2 H), 7.82 (m, 1 H), 7.66 (t, 1 H), 4.78 (s, 2 H).
Reaction SMILES: [I:1]I.[CH3:3][C:4]1[N:9]=[C:8]([NH2:10])[N:7]=[C:6]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:5]=1.[OH-].[Na+]>C(Cl)Cl.O>[I:1][C:5]1[C:6]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[N:7][C:8]([NH2:10])=[N:9][C:4]=1[CH3:3]
Reactant: II
Reactant: CCCCCNc1cc(C)nc(N)n1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CCCCCNc1nc(N)nc(C)c1I
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.4 %

Procedure:
A solution of iodine (11.92 g) in DCM (300 mL) was added to a stirred mixture of the product from step (i) (8.3 g) and sodium hydroxide (3.42 g) in water (200 mL). The reaction mixture was stirred at rt overnight. The organic layer was separated and washed with sodium metabisulfate solution, then brine. The combined organic layers were dried, and the solvent evaporated under reduced pressure. The product was purified by chromatography eluting with DCM:MeOH; 95:5 to give the subtitle compound 11 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]3)[C:14](=[O:21])[NH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].Br[CH2:23][C:24]([C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=1)=[O:25].COC1C=C(C2[C@H]3[C@H](CCCC3)C(=O)N(C)N=2)C=CC=1OC>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH2:23][C:24]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)=[O:25])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: O=C(CBr)c1ccc2ccccc2c1
Reactant: COc1ccc(C2=NNC(=O)[C@H]3CCCC[C@@H]23)cc1OC
Agent: COc1ccc(C2=NN(C)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Product: COc1ccc(C2=NN(CC(=O)c3ccc4ccccc4c3)C(=O)[C@H]3CCCC[C@@H]23)cc1OC

Procedure:
Prepared from compound 1 and α-bromo-2'-acetonaphthone as described for compound 8. Purified by chromatography [ethyl acetate: petroleum ether (60°-80° C.)/1:3]. Crystallized from methanol at -20° C. M.p. 89°-90° C.
Reaction SMILES: Cl[CH:2]([CH2:6][CH2:7][CH2:8][C:9]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13](=[O:22])[N:14]2[CH3:21])[C:3]([OH:5])=O.[NH2:23][C:24](N)=[S:25].C([O-])(=[O:29])C.[Na+]>COC(O)C>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:9]([CH2:8][CH2:7][CH2:6][CH:2]2[S:25][C:24](=[O:29])[NH:23][C:3]2=[O:5])=[C:10]2[C:15]=1[N:14]([CH3:21])[C:13](=[O:22])[CH:12]=[CH:11]2
Reactant: CC(=O)[O-]
Reactant: NC(N)=S
Reactant: COc1ccc(CCCC(Cl)C(=O)O)c2ccc(=O)n(C)c12
Agent: COC(C)O
Agent: [Na+]
Product: COc1ccc(CCCC2SC(=O)NC2=O)c2ccc(=O)n(C)c12
Temperature: 110 °C
Reaction time: 5 h
Yield: 31 %

Procedure:
1 g of 2-chloro-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)valeric acid, 380 mg of thiourea, and 380 mg of sodium acetate were added to 20 ml of methoxyethanol, followed by stirring at 110° C. for 5 hours. The reaction mixture was concentrated under reduced pressure, and water and a small amount of ethanol were added to the residue to precipitate a solid. The precipitated solid was collected by filtration. The solid collected by filtration was added to a mixed solvent of 10 ml of 10% hydrochloric acid and 10 ml of ethanol, followed by heating and refluxing overnight. The solvent was distilled off under reduced pressure, and the residue was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated. The concentrated residue was purified by silica gel column chromatography (dichloromethane:methanol of 100:1→10:1), and recrystallized from an ethanol-ether mixed solvent, giving 332 mg (29% yield) of 5-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)propyl]thiazolidine-2,4-dione as a light yellow powder.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[CH2:10][CH2:11][CH2:12][CH:3]([C:4]=23)[C:2]1=[O:13].[H-].[Na+].[Br:16][CH2:17][CH2:18]Br>CN(C)C=O>[Br:16][CH2:17][CH2:18][N:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[CH2:10][CH2:11][CH2:12][CH:3]([C:4]=23)[C:2]1=[O:13]
Reactant: BrCCBr
Reactant: O=C1Nc2cccc3c2C1CCC3
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1C2CCCc3cccc(c32)N1CCBr
Temperature: 25 °C
Reaction time: 1 h
Yield: 33.9 %

Procedure:
2a,3,4,5-Tetrahydrobenz[cd]indole-2(1H) -one (3.46 g, 20mmol) was dissolved in anhydrous N,N-dimethylformamide (20 ml). Thereto was added sodium hydride (0.8 g, 20 mmol), and the resulting solution was stirred at room temperature for 1 hour. The reaction solution was mixed with 1,2-dibromoethane (10 ml, 115 mmol) and again stirred for 1 hour. The reaction solution was extracted by adding 100 ml of ethyl acetate and 100 ml of water, and the resulting ethyl acetate layer was separated, washed with water and dried with anhydrous sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was crystallized from a dimethylformamide-water mixture to obtain 1.9 g of the title compound (34% in yield).
Reaction SMILES: [CH3:1][CH:2]([CH3:7])[CH2:3][B:4]([OH:6])[OH:5].O.O.O.O.O.O.O[C:15]([C:18](O)([CH3:20])[CH3:19])([CH3:17])[CH3:16]>CCOCC.CCCCCC>[CH3:16][C:15]1([CH3:17])[C:18]([CH3:20])([CH3:19])[O:6][B:4]([CH2:3][CH:2]([CH3:7])[CH3:1])[O:5]1
Reactant: CC(C)(O)C(C)(C)O
Reactant: CC(C)CB(O)O
Solvent: CCCCCC
Solvent: CCOCC
Solvent: O
Product: CC(C)CB1OC(C)(C)C(C)(C)O1
Reaction time: 24 h
Yield: 48.4 %

Procedure:
A solution of 50.13 g (0.494 mol) of 2-methylpropylboronic acid in 300 mL of ether, prepared by a procedure substantially similar to the foregoing, was contacted with 112.63 g (0.494 mol) of pinacol hexahydrate and stirred for 24 hours. At the end of this period, the resulting reaction mixture was diluted with 500 mL of hexane. A top layer formed which was separated from the rest of the mixture and contacted with 18 mL of water. After stirring for 15 minutes, 9.52 g of a solid separated, which was removed by filtration. The remaining hexane layer was dried over Na2SO4 and residual solvent was removed by evaporation. The remaining material was then distilled using a 6" spinning band distillation column, to obtain 43.98 g (0.239 mol, 48.4%) of an oil, bp: 65°-72°/13 mm, 1H NMR (90 MHz, CDCl3): δ0.65 (d, J=6.6 Hz, 2), 0.93 (d, J=6.6 Hz, 6), 1.25 (s, 12), 1.86 (hep, J=6.6 Hz, 1); Anal. Calcd. for C10H21O2B: C, 65.25; H, 11.50; B, 5.87; Found: C, 65.07, H, 11.52; B, 6.01.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[S:12](Cl)(=[O:14])=[O:13].C(N(CC)CC)C.[C:23]([NH2:27])([CH3:26])([CH3:25])[CH3:24].CC(C)=O>CC(C)=O.O>[C:23]([NH:27][S:12]([C:4]1[CH:5]=[CH:6][C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:3]=1[O:2][CH3:1])(=[O:14])=[O:13])([CH3:26])([CH3:25])[CH3:24]
Reactant: COc1cc([N+](=O)[O-])ccc1S(=O)(=O)Cl
Reactant: CC(C)(C)N
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC(C)=O
Product: COc1cc([N+](=O)[O-])ccc1S(=O)(=O)NC(C)(C)C
Reaction time: 5 h

Procedure:
A solution of 5.0 g (19.9 mmol) of 2-methoxy-4-nitro-benzenesulfonyl chloride in acetone/water (60 ml/15 ml) is mixed at room temperature with 2.9 ml of triethylamine and 2.2 ml of tert.-butylamine. After 5 hours, the acetone is drawn off, and the residue is extracted from ethyl acetate. The combined organic phases are washed with dilute HCl solution and saturated NaCl solution and then filtered through a Whatman filter and concentrated by evaporation. The crude product that is obtained is recrystallized from ethyl acetate. 4.2 g (14.6 mmol, corresponding to 73% of theory) of the product is obtained.
Reaction SMILES: N[C@H]([C:5](O)=[O:6])C[SeH].[Li]CCCC.[Si:13]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].CN(CCN(C)C)C.CN(C=O)C.Cl>C1COCC1>[Si:13]([O:20][C:21]1[C:22]([F:27])=[C:23]([CH:24]=[CH:25][CH:26]=1)[CH:5]=[O:6])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]
Reactant: N[C@@H](C[SeH])C(=O)O
Reactant: CC(C)(C)[Si](C)(C)Oc1ccccc1F
Agent: CN(C)CCN(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1cccc(C=O)c1F
Reaction time: 0.5 h
Yield: 74.2 %

Procedure:
Sec-BuLi (1.3M solution in cyclohexane, 75 mL, 98 mmol) was added slowly at −78° C. to a solution of Intermediate 31, 1-(tert-Butyldimethylsilyl)oxy-2-fluorobenzene (20.1 g, 89 mmol) and TMEDA (14.8 mL, 98 mmol) in THF (200 mL) and the mixture was stirred at the same temperature for 30 min. DMF (7.5 mL, 98 mmol) was added to the mixture at −78° C., and the mixture was stirred at the same temperature for 1.5 h. Then 10% aqueous HCl was added to attain pH˜4-5 (200 mL), and the reaction mixture was stirred at RT for 30 min. The organic layer was separated. Aqueous layer was extracted with EtOAc (200 mL). The organic layers was washed with sat. NaHCO3, brine, dried with Na2SO4 and evaporated in vacuo to give the title compound (16.7 g, 74%, 66 mmol) as a yellow oil. 1H NMR data (dmso-d6): 10.21 (s, 1H, CHO), 7.39-7.45 (m, 1H, H—Ar), 7.32-7.38 (m, 1H, H—Ar), 7.22-7.28 (m, 1H, H—Ar), 0.97 (s, 9H, t-Bu), 0.20 (s, 6H, 2CH3).
Reaction SMILES: CS([O:5][CH2:6][CH2:7][C:8]1[N:9]=[C:10]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[O:11][C:12]=1[CH3:13])(=O)=O.O[C:20]1[CH:29]=[C:28]2[C:23]([CH2:24][CH:25]([C:30]([O:32]C(C)(C)C)=[O:31])[CH2:26][O:27]2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CC#N.C(OCC)C>[C:23]([CH:26]1[CH:25]([C:30]([OH:32])=[O:31])[CH2:24][C:23]2[C:28](=[CH:29][C:20]([O:5][CH2:6][CH2:7][C:8]3[N:9]=[C:10]([C:14]4[S:15][CH:16]=[CH:17][CH:18]=4)[O:11][C:12]=3[CH3:13])=[CH:21][CH:22]=2)[O:27]1)([CH3:28])([CH3:24])[CH3:22]
Reactant: Cc1oc(-c2cccs2)nc1CCOS(C)(=O)=O
Reactant: CC(C)(C)OC(=O)C1COc2cc(O)ccc2C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC#N
Product: Cc1oc(-c2cccs2)nc1CCOc1ccc2c(c1)OC(C(C)(C)C)C(C(=O)O)C2
Temperature: 25 °C

Procedure:
2-(5-methyl-2-thien-2-yl-1,3-oxazol-4-yl)ethyl methanesulfonate (947 mg, 3.3 mmol), tert-butyl 7-hydroxychromane-3-carboxylate (750 mg, 3 mmol) and potassium carbonate (1.24 g, 9 mmol) were mixed in CH3CN and refluxed under N2 atmosphere overnight. After the completion of the reaction (TLC), the reaction mixture was cooled to room temperature and diluted with 30 ml of diethyl ether and passed through a small pad of silica. Silica was washed with 100 ml of ether and the ether solution was evaporated to give the product which was purified by column chromatography on silica using ethyl acetate and hexanes as eluent (699 mg, 53%).
Reaction SMILES: Cl.[NH2+:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[CH2:14][C@@H:3]12.C(N(CC)CC)C.Br[CH2:23][CH2:24][CH3:25]>CN(C)C=O>[CH2:23]([N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[CH2:14][C@@H:3]12)[CH2:24][CH3:25]
Reactant: CCCBr
Reactant: c1ccc2c(c1)C[C@H]1[NH2+]CCC[C@H]21
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCN1CCC[C@@H]2c3ccccc3C[C@H]21
Temperature: 25 °C
Reaction time: 18 h
Yield: 378.7 %

Procedure:
A solution of trans-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridinium hydrochloride (3.00 g, 14.3 mmol) and triethylamine (4.36 g, 43.1 mmol) in 95 ml of N,N-dimethylformamide was stirred at room temperature and bromopropane (1.85 g, 15.04 mmol) added dropwise. After the mixture was stirred for 18 h at room temperature, the solvent was removed and ethyl acetate/water were added. The organic layer was washed with water and dried over MgSO4. The filtrate was concentrated to give a yellow oil (11.66 g, 82%).