Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.N1([C:14](=[O:15])[C:13]2[N:11](C)C=N[C:8]=2N(C)C1=O)C.C([O-])(=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Na+].[CH:26]1(C)[CH2:31]CC(C(C)C)[CH:28]([OH:35])[CH2:27]1>O>[CH2:28]([O:35][C:14](=[O:15])[C@H:13]([CH2:8][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[NH2:11])[CH2:27][CH2:26][CH3:31]
Reactant: CC1CCC(C(C)C)C(O)C1
Reactant: Cn1c(=O)c2c(ncn2C)n(C)c1=O
Reactant: O=C([O-])c1ccccc1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCCCOC(=O)[C@@H](N)Cc1ccccc1

Procedure:
HCl (100 g) was dissolved in water (1 L). Caffeine (30 g), sodium benzoate (50 g), and menthol (30 g) were added into the mixture and the mixture was stirred for a few minutes. The mixture was filled into either spray bottles or roll-on bottles.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]2[C:9]3[CH2:14][CH2:13][NH:12][CH2:11][C:10]=3[C:15](=[O:17])[O:16][C:5]=2[CH:4]=1.C(N(CC)CC)C.Cl.Cl[CH2:27][CH2:28][N:29]1[CH2:36][CH:35]2[CH2:37][CH:31]([CH2:32][CH2:33][CH2:34]2)[CH2:30]1>>[CH:35]12[CH2:37][CH:31]([CH2:32][CH2:33][CH2:34]1)[CH2:30][N:29]([CH2:28][CH2:27][N:12]1[CH2:13][CH2:14][C:9]3[C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[O:16][C:15](=[O:17])[C:10]=3[CH2:11]1)[CH2:36]2
Reactant: COc1ccc2c3c(c(=O)oc2c1)CNCC3
Reactant: ClCCN1CC2CCCC(C2)C1
Agent: Cl
Solvent: CCN(CC)CC
Product: COc1ccc2c3c(c(=O)oc2c1)CN(CCN1CC2CCCC(C2)C1)CC3
Yield: 48.3 %

Procedure:
Prepared by the method described for Example 13 from 1,2,3,4-tetrahydro-8-methoxy-5H-[1]benzopyrano[3,4-c]pyridin-5-one (3.0 g, 0.013 moles), triethylamine (7.2 ml, 0.052 moles), and 3-(2-chloroethyl)-3-azabicyclo-[3.3.1]nonane hydrochloride (3.25 g, 0.015 moles). Recrystallization from ethanol gave the product (2.4 g), mp 102°-103° C.
Reaction SMILES: [C:1]1([C:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:16][N:17]([CH3:22])[N:18]=[CH:19][CH:20]=O.[O-]CC.[Na+].[Na]>C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:16][N:17]([CH3:22])[N:18]=[CH:19][CH:20]=[C:9]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:8]
Reactant: CN(C)N=CC=O
Reactant: O=C(Cc1ccccc1)c1ccccc1
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CN(C)N=CC=C(C(=O)c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 103.1 %

Procedure:
To a mixture of 19.6 g (0.1 mole) desoxybenzoin and 10 g (0.1 mole) of glyoxal mono(dimethylhydrazone) in 100 ml ethanol was added dropwise a solution of sodium ethoxide prepared by dissolving 2.3 g (0.1 mole) sodium metal in 100 ml ethanol. The mixture was heated at reflux for one-half hour. TLC (90/10, toluene/ethyl acetate) showed a small amount of starting desoxybenzoin, so 2.0 g (0.02 mole) of additional glyoxal mono(dimethylhydrazone) was added. Heating was continued another two hours. TLC at this time showed no starting material, and two clean close yellow product spots (isomers). The mixture was poured into 1 l ice water then extracted with methylene chloride. The organic extracts were dried and concentrated on a rotary evaporator to give 28.7 g (100%) of yellow oil. The NMR showed the presence of two major N(CH3)2 containing materials (product isomers). The crude oil crystallized from isopropanol to give one pure isomer of product, 13.4 g (48%), pale yellow crystals, m.p. 131°-2°.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH2:45]([O:47][C:48](=[O:73])[CH2:49][CH2:50][C:51]1[O:52][C:53]2[CH:72]=[CH:71][CH:70]=[CH:69][C:54]=2[C:55]=1[CH2:56][CH:57]1[CH2:61][CH2:60][CH2:59][N:58]1[C:62](=[O:68])[CH:63]([NH2:67])[CH:64]([CH3:66])[CH3:65])[CH3:46]>CN1C(=O)CCC1.C(OCC)C>[CH2:45]([O:47][C:48](=[O:73])[CH2:49][CH2:50][C:51]1[O:52][C:53]2[CH:72]=[CH:71][CH:70]=[CH:69][C:54]=2[C:55]=1[CH2:56][CH:57]1[CH2:61][CH2:60][CH2:59][N:58]1[C:62](=[O:68])[CH:63]([NH:67][C:11](=[O:13])[CH:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:10])[CH:64]([CH3:66])[CH3:65])[CH3:46]
Reactant: CCOC(=O)CCc1oc2ccccc2c1CC1CCCN1C(=O)C(N)C(C)C
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOCC
Solvent: CN1CCCC1=O
Solvent: CN1CCOCC1
Product: CCOC(=O)CCc1oc2ccccc2c1CC1CCCN1C(=O)C(NC(=O)C(C)NC(=O)OC(C)(C)C)C(C)C
Reaction time: 0.17 h

Procedure:
A solution containing Boc-L-alanine (69 mg, 0.37 mmol) in NMP (3 mL) was treated with HATU (131 mg, 0.34 mmol) followed by NMM (0.1 mL, 0.9 mmol) at ambient temperature. After 10 min, amine 50 (111 mg, 0.28 mmol) in NMP (5 mL) was added in a dropwise fashion. After 5 h, the reaction mixture was diluted with diethyl ether and washed successively with NaHCO3, 1 M HCl, water, and brine. The organic extract was dried over anhydrous Na2SO4, filtered and concentrated to afford 160 mg (quant.) of 51 which was used without further purification. 1H NMR (CDCl3, 300 MHz) δ7.81-7.78 (m, 1H), 7.38-7.36 (m, 1H), 7.28-7.21 (m, 3H), 6.86 (d, J=8.7 Hz, 1H), 5.04 (d, J=6.9 Hz, 1H), 4.61 (dd, J=6.3, 8.7 Hz, 1H), 4.48-4.42 (m, 1H), 4.22 (m, 1H), 4.13 (q, J=6.9 Hz, 2H), 3.73-3.62 (m, 2H), 3.41-3.36 (m, 2H), 3.28 (dd, J=3.0, 13.5 Hz, 1H), 3.11 (app t, J=6.9 Hz, 2H), 2.85-2.73 (m, 4H), 2.38 (app t, J=8.1 Hz, 2H), 2.13-1.98 (m, 2H), 1.80-1.64 (m, 1H), 1.45 (s, 9H), 1.37 (d, J=6.9 Hz, 3H), 1.26 (t, J=7.5 Hz, 3H), 1.03-0.95 (m, 6H) ppm. Mass spectrum: m/z 572 [M+H]+; and, 594 [M+Na]+.
Reaction SMILES: C[N:2](/[CH:4]=[C:5]1\[C:6](=O)[C:7]2[CH:8]=[N:9][N:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]=2[CH2:12][CH2:13]\1)[CH3:3].[CH3:21][O:22][C:23]1[CH:35]=[CH:34][C:26]([CH2:27][N:28]2C(N)=[CH:31][CH:30]=[N:29]2)=[CH:25][CH:24]=1.FC(F)(F)C(O)=O>O>[CH3:21][O:22][C:23]1[CH:35]=[CH:34][C:26]([CH2:27][N:28]2[C:3]3[N:2]=[CH:4][C:5]4[CH2:13][CH2:12][C:11]5[N:10]([C:14]6[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=6)[N:9]=[CH:8][C:7]=5[C:6]=4[C:31]=3[CH:30]=[N:29]2)=[CH:25][CH:24]=1
Reactant: CN(C)/C=C1/CCc2c(cnn2-c2ccccc2)C1=O
Reactant: COc1ccc(Cn2nccc2N)cc1
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Cn2ncc3c4c(cnc32)CCc2c-4cnn2-c2ccccc2)cc1
Temperature: 100 °C
Yield: 52.5 %

Procedure:
To a mixture of (Z)-5-((dimethylamino)methylene)-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-one (1 g, 3.74 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (3.5 g, 17.2 mmol) was added trifluoroacetic acid (0.8 mL, 10.3 mmol). The reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was then poured into ice-cooled water (100 mL) and extracted with dichloromethane (3×75 mL). The combined organic extracts were dried using sodium sulfate and concentrated under reduced pressure to give a dark residue. The crude product was purified by flash column chromatography (SiO2, gradient from 100% chloroform to 2% methanol in chloroform) to a residue, which was further purified by crystallization from methanol and isopropanol to give the pure desired product (0.8 g, 15%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 1H), 7.87 (s, 1H), 7.78 (s, 1H), 7.55-7.49 (m, 4H), 7.41-7.39 (m, 1H), 7.38 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 5.66 (s, 2H), 3.75 (s, 3H), 3.14-3.09 (m, 4H); LCMS [M+H]: 408.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:17]=1)[C:12]([OH:14])=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O[C:27]1[C:35]2N=NNC=2C=[CH:29][CH:28]=1.C1([N:42]=C=NC2CCCCC2)CCCCC1.C(N)CCC>C(Cl)Cl>[CH2:35]([C:15]1[C:16]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:17][C:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2])=[CH:10][C:11]=1[C:12]([NH2:42])=[O:14])[CH2:27][CH2:28][CH3:29]
Reactant: Oc1cccc2[nH]nnc12
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CC(C)(C)[Si](C)(C)Oc1cc(O[Si](C)(C)C(C)(C)C)cc(C(=O)O)c1
Solvent: ClCCl
Solvent: CCCCN
Product: CCCCc1c(O[Si](C)(C)C(C)(C)C)cc(O[Si](C)(C)C(C)(C)C)cc1C(N)=O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 90 %

Procedure:
A 50 mL round bottom flask equipped with a stirring bar and rubber septum was charged with 3,5-bis(tert-butyldimethylsilyloxy)benzoic acid (0.76 g, 2.0 mmol) and placed under argon. 15 mL dry DCM was added followed by the addition of hydroxybenzotriazole (HOBT; 0.3 g, 2.2 mmol) and N,N′-dicyclohexylcarbodiimide (DCC; 0.45 g, 2.2 mmol) in that order by partial removal of the septum. The resulting slurry was stirred at room temperature for 10 min. Butan-1-amine (0.3 mL, 0.22 g, 3.0 mmol) was then added drop wise and the reaction mixture was stirred overnight. The resulting heterogeneous solution was then filtered over a Buchner funnel and the filtrate was further diluted with DCM and washed with 0.5 M HCl. The aqueous layer was extracted once more with DCM and the combined organics were dried over Na2SO4. The crude reaction mixture was then concentrated on to silica gel via rotary evaporation and subjected to flash chromatography (SiO2, 10% EtOAc-hexanes; Rf=0.3 at 10% EtOAc-hexanes) to afford 13c as a white crystalline solid (0.76 g, 1.8 mmol): mp 114-117° C.; IR (neat) λmax 3294, 2929, 2857, 1632, 1583, 1543, 1438, 1334, 1253, 1163, 1027, 1004, 935, 829, 778, 692, 667, 486 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.81 (d, J=2.1 Hz, 2H), 6.43 (t, J=2.1 Hz, 1H), 6.02 (app s, 1H), 3.41 (q, J=7.1 Hz, 2H), 1.58 (p, J=7.7 Hz, 2H), 1.39 (sex, J=7.2 Hz, 2H), 0.97 (s, 18H), 0.95 (t, J=7.3 Hz, 3H), 0.19 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 167.3, 156.8, 137.1, 114.9, 112.1, 39.9, 31.8, 25.8, 20.3, 18.3, 13.9, −4.3; LRMS (EI) m/z=437.3 [M]+.
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](Cl)=[N:7]2.[CH3:13][O:14][C:15]1[CH:23]=[C:22]2[C:18]([CH2:19][CH2:20][CH:21]2[NH2:24])=[CH:17][CH:16]=1.[O:25]=[S:26]1(=[O:32])[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27]1>>[O:25]=[S:26]1(=[O:32])[CH2:30][CH2:29][CH:28]([NH:31][C:2]2[C:3]3[CH:4]=[CH:5][C:6]([NH:24][CH:21]4[C:22]5[C:18](=[CH:17][CH:16]=[C:15]([O:14][CH3:13])[CH:23]=5)[CH2:19][CH2:20]4)=[N:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)[CH2:27]1
Reactant: NC1CCS(=O)(=O)C1
Reactant: Clc1ccc2c(I)cccc2n1
Reactant: COc1ccc2c(c1)C(N)CC2
Product: COc1ccc2c(c1)C(Nc1ccc3c(NC4CCS(=O)(=O)C4)cccc3n1)CC2

Procedure:
The title compound, MS: m/e=424.3 (M+H+), was prepared in accordance with the general method of example 1 from 5-iodo-2-chloroquinoline, 6-methoxyindan-1-ylamine (CAS 103028-81-5) and 1,1-dioxido-tetrahydrothien-3-ylamine.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6].[CH3:13][C:14](=[CH2:18])[CH2:15][Mg]Cl>C1COCC1>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([OH:6])[CH2:15][C:14]([CH3:18])=[CH2:13]
Reactant: O=C(CCCCl)c1ccccc1
Reactant: C=C(C)C[Mg]Cl
Solvent: C1CCOC1
Product: C=C(C)CC(O)(CCCCl)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
To a solution of compound 4-chloro-1-phenylbutan-1-one (3.64 g, 0.02 mol) in THF (60 mL) was added (2-methylallyl)magnesium chloride (60 mL, 1 mol/L) at −78° C. The mixture was stirred at room temperature for 1 h. TLC showed the disappearance of the starting material. The mixture was quenched with satd aq NH4Cl and extracted with EtOAc. The combined organic phase was dried over Na2SO4 and concentrated to give the crude final product, which was purified by chromatography to afford the compound 7-chloro-2-methyl-4-phenylhept-1-en-4-ol (4.2 g, 90%).
Reaction SMILES: CO[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.P(Br)(Br)[Br:18].O.[OH-].[Na+]>CN(C=O)C>[Br:18][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1
Reactant: BrP(Br)Br
Reactant: COC(=O)c1ccc2nccc(OC)c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2nccc(Br)c2c1
Temperature: 80 °C

Procedure:
To a solution of methyl 4-methoxy-6-quinolinecarboxylate (910 mg) in DMF (7 ml) was added phosphorus tribromide (1.57 ml) while stirring under ice-cooling. DMF (7 ml) was added and the mixture was heated at 80° C. for 3 hr. To the reaction mixture was added water (50 ml) and the reaction mixture was made weak basic with a 1N aqueous sodium hydroxide solution. The resulting precipitate was collected by filtration and purified by silica gel column chromatography (eluent: chloroform-methanol=100/0-100/1) to give the object compound (420 mg) as a yellow powder.
Reaction SMILES: C(N(CC)CC)C.Cl.[NH2:9][C@@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]1.[CH3:20][C:21]([S:24](Cl)=[O:25])([CH3:23])[CH3:22].Cl>C(OCC)(=O)C>[CH3:20][C:21]([S:24]([NH:9][C@@H:10]1[CH2:11][CH2:12][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:14][CH2:15]1)=[O:25])([CH3:23])[CH3:22]
Reactant: CC(C)(C)S(=O)Cl
Reactant: COC(=O)[C@H]1CC[C@@H](N)CC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: COC(=O)[C@H]1CC[C@@H](NS(=O)C(C)(C)C)CC1

Procedure:
Triethylamine (272 mL) was added dropwise to a suspension of methyl cis-4-amino-1-cyclohexane carboxylate hydrochloride (7) (151 g, 0.78 mol) and 2-methylpropane-2-sulfinyl chloride (3) (120.8 g, 1.1 eq) in ethyl acetate (755 mL) at 6 to 9° C. The mixture was stirred for an hour at the same temperature and poured into diluted hydrochloric acid. The mixture was extracted with ethyl acetate (750 mL×2) and each of organic layers was washed with water, 5% aqueous solution of sodium bicarbonate, water and brine, successively. The solvent was concentrated under reduced pressure to obtain oily (14) (222.7 g, 1.09%).
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:6]=1[CH:7]=[O:8].[CH:15]1([Mg]Br)[CH2:19][CH2:18][CH2:17][CH2:16]1.O1CCCC1.Cl.O>O1CCCC1>[CH:15]1([CH:7]([C:6]2[CH:5]=[C:4]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[O:3][C:2]=2[CH3:1])[OH:8])[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Cc1oc(-c2ccccc2)cc1C=O
Reactant: Br[Mg]C1CCCC1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: Cc1oc(-c2ccccc2)cc1C(O)C1CCCC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
To a solution of 2-methyl-5-phenylfuran-3-carbaldehyde (1.3 g) in tetrahydrofuran (30 mL) was added dropwise 1N cyclopentylmagnesium bromide-tetrahydrofuran solution (10.5 mL) at 0° C. and, after the completion of the dropwise addition, the mixture was stirred at 0° C. for 1 hr. The reaction mixture was treated with 1N hydrochloric acid, poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column (0% ethyl acetate/hexane to 20% ethyl acetate/hexane) to give the title compound (0.9 g, 50%) as a white crystal.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7]C#N)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].Cl.[NH2:17][OH:18].[C:19](=[O:22])([O-])[O-].[Na+].[Na+].C(O)C>O>[Cl:1][C:2]1[CH:11]=[CH:10][C:5](/[CH:6]=[CH:7]/[C:19]([NH2:17]=[O:18])=[O:22])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13]
Reactant: NO
Reactant: N#CC=Cc1ccc(Cl)c(C(F)(F)F)c1
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=C(/C=C/c1ccc(Cl)c(C(F)(F)F)c1)[NH2+][O-]
Yield: 39.9 %

Procedure:
12.1 g (0.05 mol) of 4-chloro-3-trifluoromethyl-cinnamonitrile are added to a solution of 7.2 g (0.10 mol) of hydroxylamine hydrochloride, 7.3 g (0.10 mol) of sodium carbonate in 100 ml of water, and 100 ml of ethanol. The mixture is refluxed until the reaction is complete (24 hours) and the entire batch is subsequently stirred into 250 ml of water. The solid which separates out during this process is filtered off with suction, washed with a little water and dried. 5.3 g (39.3% of theory) of (E)-4-chloro-3-trifluoromethyl-cinnamamide oxide are obtained.
Reaction SMILES: [CH2:1]([N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][CH2:10]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCCCCC.S(Br)([Br:27])=O.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:1]([N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][CH2:10][Br:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCCN(Cc1ccccc1)Cc1ccccc1
Reactant: O=S(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: BrCCN(Cc1ccccc1)Cc1ccccc1
Reaction time: 15 h
Yield: 55 %

Procedure:
To N,N-dibenzyl-2-aminoethanol (18.47 g) was added hexane (150 ml) and DMF (0.3 ml), and thereto was added dropwise thionyl bromide (15.91 g) at 0° C. The mixture was stirred for 15 hours, and to the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution in an ice-bath, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (×2) and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (the developing solvent: hexane) to give the title compound (12.80 g).
Reaction SMILES: [F:1][C:2]([F:19])([CH3:18])[CH2:3][N:4]1[CH2:10][CH2:9][C:8]2[CH:11]=[C:12]([NH2:17])[C:13]([O:15][CH3:16])=[CH:14][C:7]=2[CH2:6][CH2:5]1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=2[C:30]([NH:32][CH3:33])=[O:31])[C:24]([Cl:38])=[CH:23][N:22]=1>>[Cl:38][C:24]1[C:25]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=2[C:30]([NH:32][CH3:33])=[O:31])=[N:26][C:21]([NH:17][C:12]2[C:13]([O:15][CH3:16])=[CH:14][C:7]3[CH2:6][CH2:5][N:4]([CH2:3][C:2]([F:1])([F:19])[CH3:18])[CH2:10][CH2:9][C:8]=3[CH:11]=2)=[N:22][CH:23]=1
Reactant: CNC(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: COc1cc2c(cc1N)CCN(CC(C)(F)F)CC2
Product: CNC(=O)c1ccccc1Nc1nc(Nc2cc3c(cc2OC)CCN(CC(C)(F)F)CC3)ncc1Cl

Procedure:
The title compound was prepared from 3-(2,2-Difluoro-propyl)-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide in an analogous manner to Example 61e. Product isolated as a pale yellow solid (0.019 g, 21%). MP: 162-165° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 11.00-10.97 (m, 1H), 8.68-8.64 (m, 1H), 8.11 (d, 1H, J=1.8 Hz), 8.09-8.07 (m, 1H), 7.54-7.39 (m, 3H), 7.11-7.06 (m, 1H), 6.64 (s, 1H), 6.18 (br s, 1H), 3.87 (d, 3H, J=1.5 Hz), 3.06-3.02 (m, 3H), 2.90-2.72 (m, 10H), 1.75-1.61 (m, 3H). MS: 531.17 (MH)+.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Se:9](=[O:16])[CH2:8]1>C(Cl)(Cl)Cl>[Cl:3][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Se:9](=[O:16])[CH2:8]1
Reactant: O=S(Cl)Cl
Reactant: O=[Se]1CN(CO)c2ccccc21
Solvent: ClC(Cl)Cl
Product: O=[Se]1CN(CCl)c2ccccc21

Procedure:
0.55 cm3 of thionyl chloride (0.02 mol) is added dropwise and with stirring into a round-bottom flask containing 0.01 mol of 3-(hydroxymethyl)benzoselenazolinone dissolved in 100 cm3 of chloroform. The mixture is brought to reflux for 2 hours and the chloroform is then evaporated off under reduced pressure. The product is recrystallized in cyclohexane.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)=[O:5].[CH3:19]I.[Mg].S(=O)(=O)(O)O>C1COCC1.CCOCC.O>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:9]2[CH:10]=[CH:11][C:6]([C:4]([OH:5])([CH3:19])[CH2:3][CH2:2][NH2:1])=[CH:7][CH:8]=2)=[CH:17][CH:16]=1
Reactant: CI
Reactant: NCCC(=O)c1ccc(-c2ccc(F)cc2)cc1
Agent: O=S(=O)(O)O
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: CC(O)(CCN)c1ccc(-c2ccc(F)cc2)cc1

Procedure:
A solution of 24.4 g of 1-amino-3-(4'-fluoro-4-biphenylyl)-propan-3-one [obtainable by reacting 1-chloro-3-(4'-fluoro-4-biphenylyl)-propan-3-one with potassium phthalimide and subsequent hydrolysis] in 200 ml of THF is added dropwise, while stirring, at 20° to a Grignard solution prepared from 30 g of CH3I and 5 g of magnesium in 1000 ml of ether. The mixture is stirred for a further 4 hours, the resulting alcoholate is decomposed by means of water and dilute sulfuric acid, and the mixture is worked up in the customary manner to give 3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p. 144°-146°.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([SH:19])=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].C(O)CO>[Cu]I.CC(O)C>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)=[CH:15][CH:14]=1
Reactant: Ic1ccc2[nH]ccc2c1
Reactant: COc1ccc(S)cc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Product: COc1ccc(Sc2ccc3[nH]ccc3c2)cc1
Yield: 89.3 %

Procedure:
The general procedure in example 39 was followed. 5-Iodoindole (243 mg, 1.0 mmol), 4-methoxythiophenol (123 μL, 1.0 mmol), CuI (10 mg, 0.05 mmol), K2CO3 (276 mg, 2.0 mmol), ethylene glycol (111 μL, 2.0 mmol) and 2-propanol (1.0 mL) were used to obtain the 5-(4-methoxyphenyl)sulfanylindole (228 mg, 90% yield) as white solid. Column chromatographic solvent (hexane/ethyl acetate=5/1). Rf=0.3 (hexane/ethyl acetate=5/1). 1H NMR (CDCl3, 300 MHz) δ 8.14 (brs, 1 H), 7.69 (s, 1 H), 7.30 (d, 1 H, J=8.4 Hz), 7.12-7.28 (m, 4 H), 6.79 (dt, 2 H, J=2.1 Hz, 9.0 Hz), 6.47-6.49 (m, 1 H), 3.76 (s, 3 H). 13C NMR (CDCl3, 75 MHz) δ 158.7, 135.2, 132.1, 128.9, 128.8, 126.5, 126.2, 125.2, 124.9, 114.8, 112.1, 102.9, 55.7. IR (neat, cm−1) 3417 (broad), 2958, 2939, 2834. MS (EI) m/z (relative intensity) 255 (100), 223 (15). HRMS (EI), Cald. for C15H13NOS 255.0712. Found 255.0702. Anal. Cald. for C15H13NOS, Cald. C, 70.56; H, 5.13. Found C, 70.37; H, 5.09.
Reaction SMILES: [CH3:1][N:2]([CH3:23])[C:3]([CH2:5][CH2:6][CH2:7][CH:8]=[CH:9][C:10]1[CH:11]=[C:12]([CH:20]=[CH:21][CH:22]=1)[C:13]([NH:15][CH:16]([CH3:19])[CH2:17][OH:18])=[O:14])=[O:4].CN(C)C(CCCCCC1C=C(C=CC=1)C(NC(C)CO)=O)=O>>[CH3:23][N:2]([CH3:1])[C:3]([CH2:5][CH2:6][CH2:7][C:8]#[C:9][C:10]1[CH:11]=[C:12]([CH:20]=[CH:21][CH:22]=1)[C:13]([NH:15][CH:16]([CH3:19])[CH2:17][OH:18])=[O:14])=[O:4]
Reactant: CC(CO)NC(=O)c1cccc(C=CCCCC(=O)N(C)C)c1
Agent: CC(CO)NC(=O)c1cccc(CCCCCC(=O)N(C)C)c1
Product: CC(CO)NC(=O)c1cccc(C#CCCCC(=O)N(C)C)c1

Procedure:
The alkyne 8 (0.100 g, 0.3 mmol) was synthesized by Lindlar catalyzed reduction using method E to obtain a mixture of 16 and 3-(5-dimethylcarbamoyl-pentyl)-N-(2-hydroxy-1-methyl-ethyl)-benzamide (13) which were separated by reverse-phase HPLC chromatography (20% acetonitrile/80% water 20 min isocratic program)(16, 34 mg).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH:19]1([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[N:27]([CH2:38][C:39]#[CH:40])[C:26]=2[C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][C:42]=2[CH2:49][O:50][Si](C(C)C)(C(C)C)C(C)C)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1.CCOC(C)=O>[CH:19]1([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[N:27]([CH2:38][C:39]#[CH:40])[C:26]=2[C:41]2[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][C:42]=2[CH2:49][OH:50])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: C#CCn1c(-c2ccc(OC)cc2CO[Si](C(C)C)(C(C)C)C(C)C)c(C2CCCCC2)c2ccc(C(=O)OC)cc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C#CCn1c(-c2ccc(OC)cc2CO)c(C2CCCCC2)c2ccc(C(=O)OC)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
Tetrabutylammonium fluoride (1.3 eq., 1M solution in THF) was added dropwise to an ice cooled solution of methyl 3-cyclohexyl-2-(4-methoxy-2-{[(triisopropylsilyl)oxy]methyl}phenyl)-1-prop-2-yn-1-yl-1H-indole-6-carboxylate in THF (0.036M). The mixture was stirred at 0° C. for 1 h then diluted with EtOAc, washed with saturated aq. NH4Cl, water and brine. The organic phase was dried over Na2SO4 and evaporated in vacuo. The residual material was subjected to flash chromatography (PE:EtOAc, 3:1). After evaporation of the solvent the product was obtained as white solid (64%). MS (ES+): 432.5 (M+H+).