Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH:4]([NH:6][CH:7]1[CH2:12][C:11]([CH3:14])([CH3:13])[NH:10][C:9]([CH3:16])([CH3:15])[CH2:8]1)[CH3:5].[CH3:18][C:19]1([CH3:28])[CH2:24]C(O)[CH2:22][C:21]([CH3:27])([CH3:26])[NH:20]1.[NH2-].[Li+].CO>CCCCCCC>[CH3:18][C:19]1([CH3:28])[CH2:24][CH:1]([O:2][C:3](=[O:17])[CH:4]([NH:6][CH:7]2[CH2:8][C:9]([CH3:16])([CH3:15])[NH:10][C:11]([CH3:14])([CH3:13])[CH2:12]2)[CH3:5])[CH2:22][C:21]([CH3:27])([CH3:26])[NH:20]1
Reactant: COC(=O)C(C)NC1CC(C)(C)NC(C)(C)C1
Reactant: CC1(C)CC(O)CC(C)(C)N1
Agent: [Li+]
Agent: [NH2-]
Solvent: CO
Solvent: CCCCCCC
Product: CC(NC1CC(C)(C)NC(C)(C)C1)C(=O)OC1CC(C)(C)NC(C)(C)C1
Yield: 76.2 %

Procedure:
To the same flask as used in Example 1 were added 24.4 g (0.1 mole) of N-(2,2,6,6-tetramethyl-4-piperidinyl)aminopropionic acid methyl ester, 17.3 g (0.11 mole) of 2,2,6,6-tetramethyl-4-piperidinol, 0.23 g of lithium amide and 100 g of heptane. The temperature was raised with stirring, and reaction was carried out at 98° to 105° C. for 6 hours, during which methanol was removed from the reaction system by means of the Deanstark trap. After completion of the reaction, water was added to the reaction solution to dissolve the product in the heptane layer. The heptane layer was separated, and heptane in the layer was removed by distillation to obtain 28 g of N-(2,2,6,6-tetramethyl-4-piperidinyl)aminopropionic acid (2,2,6,6-tetramethyl-4-piperidinyl)ester as a pale yellow liquid. Yield, 73.5% based on N-(2,2,6,6-tetramethyl-4-piperidinyl)aminopropionic acid methyl ester. A pale yellow oily product was obtained by the subsequent column chromatographic separation.
Reaction SMILES: [N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:54])[CH:14]([NH:34][C:35]([N:37]3[CH2:42][CH2:41][CH:40]([N:43]4[CH2:52][C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[NH:45][C:44]4=[O:53])[CH2:39][CH2:38]3)=[O:36])[CH2:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21](S(CC[Si](C)(C)C)(=O)=O)[CH:20]=[CH:19]4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+]>C(#N)C>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:54])[CH:14]([NH:34][C:35]([N:37]3[CH2:42][CH2:41][CH:40]([N:43]4[CH2:52][C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[NH:45][C:44]4=[O:53])[CH2:39][CH2:38]3)=[O:36])[CH2:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][CH:20]=[CH:19]4)[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: C[Si](C)(C)CCS(=O)(=O)n1ccc2cc(CC(NC(=O)N3CCC(N4Cc5ccccc5NC4=O)CC3)C(=O)N3CCC(N4CCCCC4)CC3)ccc21
Agent: [Cs+]
Agent: [F-]
Solvent: CC#N
Product: O=C(NC(Cc1ccc2[nH]ccc2c1)C(=O)N1CCC(N2CCCCC2)CC1)N1CCC(N2Cc3ccccc3NC2=O)CC1
Temperature: 80 °C
Yield: 70 %

Procedure:
A mixture of 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid {2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indol-5-ylmethyl]-ethyl}-amide (52 mg, 0.067 mmol), cesium fluoride (51 mg, 0.33 mmol) in acetonitrile (5 mL) was heated at 80° C. for 4 h. The solvents were removed in vacuo and the residue was subjected to chromatography on silica gel using methylene chloride/methanol/triethylamine (93:5:2) as eluent to afford the title compound as a white solid (70% yield). 1H-NMR (CD3CN, 500 MHz) δ 9.30 (s, 1H), 7.48 (s, 1H), 7.42 (s, 1H), 7.39 (d, J=8.2 Hz, 0.6H), 7.36 (d, J=8.2 Hz, 0.4H), 7.24-7.21 (m, 1H), 7.19 (t, J=7.9 Hz, 1H), 7.12-7.09 (m, 1H), 7.06 (d, J=8.2 Hz, 0.6H), 7.02 (d, J=8.2 Hz, 0.4H), 6.95 (t, J=7.4 Hz, 1, 4.04-3.93 (m, 1H), 3.07-3.02 (m, 1.6H), 2.95 (dd, J=13.7, 7.1 Hz, 0.4H), 2.85-2.72 (m, 3H), 2.56-2.37 (m, 3H), 2.42-2.37 (m, 1H), 1.99-1.95 (m, 7H), 1.76-1.51 (m, 8H), 1.45-1.40 (m, 3H). LC/MS: tR=1.91 min, 612.44 (MH)+.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH2:12][CH2:13][CH3:14])=[N:7]2.[NH2:15][C:16]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:17]=1[O:18][C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22]([NH2:24])=[O:23]>C(O)C>[Cl:32][C:30]1[CH:29]=[CH:28][C:17]([O:18][C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([NH2:24])=[O:23])=[C:16]([NH:15][C:2]2[C:3]3[C:8](=[N:7][C:6]([CH2:12][CH2:13][CH3:14])=[CH:5][CH:4]=3)[N:9]=[CH:10][CH:11]=2)[CH:31]=1
Reactant: CCCc1ccc2c(Cl)ccnc2n1
Reactant: NC(=O)c1cccc(Oc2ccc(Cl)cc2N)c1
Solvent: CCO
Product: CCCc1ccc2c(Nc3cc(Cl)ccc3Oc3cccc(C(N)=O)c3)ccnc2n1

Procedure:
The product from Example 2g (140 mg, 0.68 mmol) was reacted with the product from Example 171b (178 mg, 0.68 mmol) in ethanol (5 mL) at 85° C. in a sealed tube for 18 h giving the crude title compound which was purified by HPLC with TFA providing the product as the trifluoroacetic acid (110 mg, 30%). 1H NMR (500 MHz, DMSO-d6) δ ppm: 8.81 (d, J=8.54 Hz, 1H) 8.45 (d, J=7.32 Hz, 1H) 6.76-6.79 (m, 2H) 6.64 (d, J=8.54 Hz, 2H) 6.44 (s, 1H) 6.37 (t, J=7.93 Hz, 1H) 6.31 (d, J=8.54 Hz, 1H) 7.16 (dd, J=7.93, 2.44 Hz, 1H) 6.84 (d, J=7.32 Hz, 1H) 2.95 (t, J=7.32 Hz, 2H) 1.80 (m, 2H) 0.95 (t, J=7.32 Hz, 3H); MS (ESI+) m/z 433 (M+H)+.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH3:9])[CH2:3]1.[CH2:10]([NH:28][C:29]([O:31][CH2:32][CH:33]([CH2:36][O:37][C:38](OC1C=CC=CC=1)=[O:39])[O:34][CH3:35])=[O:30])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>>[CH2:10]([NH:28][C:29]([O:31][CH2:32][CH:33]([CH2:36][O:37][C:38](=[O:39])[NH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH3:9])[CH2:3]1)[O:34][CH3:35])=[O:30])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCN1CCCC(N)C1
Reactant: CCCCCCCCCCCCCCCCCCNC(=O)OCC(COC(=O)Oc1ccccc1)OC
Product: CCCCCCCCCCCCCCCCCCNC(=O)OCC(COC(=O)NC1CCCN(CC)C1)OC
Temperature: 60 °C

Procedure:
3-Amino-1-ethylpiperidine (1 ml) was added to 1.3 g of 1-octadecylcarbamoyl-2-methyl-3-phenoxycarbonylglycerol, and the reaction solution was heated at 60° C. for 1 hour and purified by silica gel chromatography [ethyl acetate-methanol (10:1)] to give 1.13 g of the objective compound as a milk-white solid.
Reaction SMILES: Br[C:2]1[N:7]2[CH:8]=[C:9]([CH3:11])[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.O.O.O.C([O-])(=O)C.[Na+].[C:20]([O:24][CH2:25][CH3:26])(=[O:23])[CH:21]=[CH2:22].O>CN(C)C(=O)C>[CH3:11][C:9]1[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=[C:2](/[CH:22]=[CH:21]/[C:20]([O:24][CH2:25][CH3:26])=[O:23])[N:7]2[CH:8]=1
Reactant: C=CC(=O)OCC
Reactant: Cc1cn2c(Br)cccc2n1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CCOC(=O)/C=C/c1cccc2nc(C)cn12
Temperature: 100 °C
Reaction time: 24 h
Yield: 55 %

Procedure:
To a solution of 5-bromo-2-methylimidazo[1,2-a]pyridine (5.00 g, 23.7 mmol) in N,N-dimethylacetamide (60 mL) were added sodium acetate trihydrate (3.89 g, 47.4 mmol), ethyl acrylate (3.10 mL, 28.4 mmol) and [1,1′bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (1.73 g, 2.37 mmol) at room temperature, and the mixture was stirred under nitrogen stream at 100° C. for 24 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80) to give the title compound (3.00 g, yield 55%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])=[C:5]2[C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1.[CH:29]12[O:36][CH:33]([CH2:34][CH2:35]1)[CH2:32][NH:31][CH2:30]2>>[F:16][C:14]([F:15])([F:17])[C:13]([C:6]1[C:7]([CH3:12])=[N:8][C:9]2[C:4]([C:5]=1[C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:26])=[O:27])=[CH:21][CH:20]=1)=[CH:3][C:2]([N:31]1[CH2:30][CH:29]3[O:36][CH:33]([CH2:34][CH2:35]3)[CH2:32]1)=[CH:11][CH:10]=2)=[O:18]
Reactant: Cc1nc2ccc(Br)cc2c(-c2ccc(S(C)(=O)=O)cc2)c1C(=O)C(F)(F)F
Reactant: C1CC2CNCC1O2
Product: Cc1nc2ccc(N3CC4CCC(C3)O4)cc2c(-c2ccc(S(C)(=O)=O)cc2)c1C(=O)C(F)(F)F
Yield: 61 %

Procedure:
The title compound was prepared from 1-[6-bromo-4-(4-methanesulfonyl-phenyl)-2-methyl-quinolin-3-yl]-2,2,2-trifluoro-ethanone [example 23] and 8-oxa-3-aza-bicyclo[3.2.1]octane according to the procedure of example 51. Yield: 61%; MS: m/z=505 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8]Cl)=[N:6][CH:7]=1.[CH3:10][S-:11].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][S:11][CH3:10])=[N:6][CH:7]=1
Reactant: ClCc1ccc(Br)cn1
Reactant: C[S-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSCc1ccc(Br)cn1
Temperature: 0 °C
Reaction time: 2 h
Yield: 81 %

Procedure:
To the stirred solution of 5-Bromo-2-chloromethyl-pyridine (3.5 gm, 16.99 mmol) in DMF (25 mL) at 0° C. is added Sodium thiomethoxide (1.31 gm, 18.68 mmol) resulting reaction mixture is stirred at 0° C. for 2 h. After completion quenched with water and extracted with ethyl acetate (3×100 mL). The Combined organic layer is washed with brine and organic layer dried over sodium sulphate, evaporate under reduced pressure. The crude is purified by column chromatography using silica 100-200 mesh using 10% EtOAc: Hexane as eluent to afford title compound (3 g) as brown colored liquid. 1NMR (400 MHz, DMSO) δ: 2.00 (s, 3H), 3.75 (s, 2H), 7.39 (d, J=8.32 Hz, 1H), 7.99-8.02 (dd, J1=2.44 Hz, J2=8.32 Hz, 1H), 8.60 (d, J=2.28 Hz, 1H). LC-MS (m/z): M+H=220.1.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[S:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:13]I>CS(C)=O>[CH3:13][O:1][C:2]1[CH:3]=[C:4]2[S:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1
Reactant: CI
Reactant: Oc1cnc2ccsc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1cnc2ccsc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 78.5 %

Procedure:
To a solution of 6-hydroxythieno[3,2-b]pyridine (2.45 g, 16.2 mmol) in dry dimethylsulfoxide (15 ml), under a nitrogen atmosphere, was added 60% sodium hydride in mineral oil (0.75 g, 19 mmol) and let stir at room temperature for 1 hour. Methyl iodide (1.25 ml, 21 mmol) was added to this solution and it was stirred for an additional two hours. The solution was poured into ice/water and extracted with diethyl ether, washed with water, dried over anhydrous sodium sulfate, filtered and carefully evaporated to give an oily product (2.1 g, 78% yield) which was used as is.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13].[CH3:16][CH:17]1[O:22][CH:21]([CH3:23])[CH2:20][NH:19][CH2:18]1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:23][CH:21]1[O:22][CH:17]([CH3:16])[CH2:18][N:19]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:20]1
Reactant: CC1CNCC(C)O1
Reactant: COC(=O)CCCCCCCCCCBr
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COC(=O)CCCCCCCCCCN1CC(C)OC(C)C1

Procedure:
This intermediate (12.0 g.) was prepared using the procedure described in Example 4a except using 12 g. (0.045 mole) of methyl 11-bromoundecylate, 5.5 ml. (0.045 mole) of 2,6-dimethylmorpholine, 6.12 ml. of triethylamine, and 15 ml. of toluene and was isolated as a yellow, viscous liquid.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]([OH:14])(=[O:13])[C:10]([CH3:12])=[CH2:11]>>[CH:1]([CH2:12][C:10](=[CH2:11])[C:9]([OH:14])=[O:13])=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=C(C)C(=O)O
Reactant: C=Cc1ccccc1
Product: C=C(CC=Cc1ccccc1)C(=O)O

Procedure:
In a similar manner to that employed for the copolymer (a-2-1), except that the charged amounts of styrene and methacrylic acid were changed to 70.4% by mass and 9.6% by mass, respectively, a styrene-methacrylic acid copolymer (a-2-3) was obtained.
Reaction SMILES: Br[CH2:2][C:3]1[C:11]2[O:10][CH:9]=[CH:8][C:7]=2[CH:6]=[C:5]([N+:12]([O-:14])=[O:13])[CH:4]=1.[CH3:15][CH:16]1[CH2:21][NH:20][CH2:19][CH2:18][NH:17]1>>[CH3:15][CH:16]1[NH:17][CH2:18][CH2:19][N:20]([CH2:2][C:3]2[C:11]3[O:10][CH:9]=[CH:8][C:7]=3[CH:6]=[C:5]([N+:12]([O-:14])=[O:13])[CH:4]=2)[CH2:21]1
Reactant: O=[N+]([O-])c1cc(CBr)c2occc2c1
Reactant: CC1CNCCN1
Product: CC1CN(Cc2cc([N+](=O)[O-])cc3ccoc23)CCN1
Yield: 95 %

Procedure:
The title compound was prepared according to the procedure of Example 112, Step 1, starting from 7-(bromomethyl)-5-nitro-1-benzofuran (120 mg, 70 mol %, 0.39 mmol; Intermediate 64) and 2-methylpiperazine (196 mg, 1.95 mmol). The crude product was purified by flash chromatography (eluent: 4% MeOH, 1% NEt3 in DCM). The title compound (102 mg, 87%) was obtained as a light yellow sticky oil. HPLC 99%, RT=1.60 min (System A; 5-60% MeCN over 3 min), 100%, RT=1.40 min (System B; 5-60% MeCN over 3 min). MS (ESI+) for C14H17N3O3 m/z 276 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)(=[O:10])=[O:9].Cl[C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][N:19]=1>>[Cl:24][C:23]1[C:18]([N:14]2[CH2:15][CH2:16][CH:11]([S:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])(=[O:9])=[O:10])[CH2:12][CH2:13]2)=[N:19][CH:20]=[CH:21][CH:22]=1
Reactant: Clc1cccnc1Cl
Reactant: O=S(=O)(c1ccccc1Cl)C1CCNCC1
Product: O=S(=O)(c1ccccc1Cl)C1CCN(c2ncccc2Cl)CC1
Yield: 51.1 %

Procedure:
Using the procedure from Example 7A, 4-[(2-chlorophenyl)sulfonyl]piperidine (150 mg, 0.58 mmol) was reacted with 2,3-dichloropyridine (173 mg, 1.16 mmol) to afford the title compound (110 mg), a white solid, in 51% yield.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:19])[N:8]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:20]=O.[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][C:26](=[O:32])[NH:27]2>>[Br:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[C:25](=[CH:20][C:3]1[NH:4][C:5]3[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]4[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]4)[C:7](=[O:19])[C:6]=3[C:2]=1[CH3:1])[C:26](=[O:32])[NH:27]2
Reactant: O=C1Cc2c(Br)cccc2N1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Product: Cc1c(C=C2C(=O)Nc3cccc(Br)c32)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Yield: 84.9 %

Procedure:
The title compound was prepared under the same conditions as described in Example 25 with 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-bromo-1,3-dihydro-indol-2-one (prepared according to US20030225127) as starting materials to give 2-(4-bromo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-5-(2-piperidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (58 mg, 84.9%) as a yellow solid.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12](O)=O)[CH:10]=2)[NH:5][C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH2:54]([O:56][C:57](=[O:72])[C:58]1[CH:63]=[CH:62][C:61]([NH:64][CH:65]2[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]2)=[C:60]([NH2:71])[CH:59]=1)[CH3:55]>CN(C=O)C>[CH2:54]([O:56][C:57]([C:58]1[CH:63]=[CH:62][C:61]2[N:64]([CH:65]3[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70]3)[C:12]([C:9]3[CH:10]=[C:11]4[C:6](=[CH:7][CH:8]=3)[NH:5][C:4]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:3][C:2]4=[O:1])=[N:71][C:60]=2[CH:59]=1)=[O:72])[CH3:55]
Reactant: O=C(O)c1ccc2[nH]c(-c3ccccc3)cc(=O)c2c1
Reactant: CCOC(=O)c1ccc(NC2CCCCC2)c(N)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1ccc2c(c1)nc(-c1ccc3[nH]c(-c4ccccc4)cc(=O)c3c1)n2C1CCCCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 800.1 %

Procedure:
4-Oxo-2-phenyl-1,4-dihydro-quinoline-6-carboxylic acid (2.78 g, 1.05 mmol) was dissolved in DMF (50 mL), and HATU (1.1 eq.) and diisopropyl ethylamine (2.2 eq, 402 μL) were added. After stirring at room temperature for 15 minutes, 3-amino-4-cyclohexylamino-benzoic acid ethyl ester (2.89 g, 1.1 eq.) dissolved in 20 mL DMF was added. After stirring overnight, the reaction was evaporated, dissolved in ethyl acetate and washed with water and brine, dried with sodium sulfate, evaporated and dried overnight. The product was then refluxed in acetic acid for 4 hr, evaporated to dryness, and coevaporated 2 more times with toluene. The product was recrystallized from methanol to give 4.13 g of product.
Reaction SMILES: [C:1](OC)(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[C:16]([Si:20]([CH3:42])([CH3:41])[O:21][CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31](=[O:40])[CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[CH:27][CH:26]=1)([CH3:19])([CH3:18])[CH3:17]>C1COCC1>[C:16]([Si:20]([CH3:42])([CH3:41])[O:21][CH2:22][CH2:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]2([CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:40][C:1](=[O:6])[CH:2]=[C:3]([OH:4])[CH2:5]2)=[CH:29][CH:30]=1)([CH3:18])([CH3:17])[CH3:19]
Reactant: COC(=O)CC(C)=O
Reactant: CC(C)(C)[Si](C)(C)OCCOc1ccc(C(=O)CCc2ccccc2)cc1
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCCOc1ccc(C2(CCc3ccccc3)CC(O)=CC(=O)O2)cc1

Procedure:
The title compound was prepared as described in General Methods 6 and 7 using 2.5 mL (23.2 mmol) of methyl acetoacetate, 0.96 g (24 mmol) of 60% sodium hydride, 15 mL (24 mmol) of 1.6M n-butyllithium, 4.5 g (11.7 mmol) of 1-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxyl -phenyl}-3-phenyl-propan-1-one from Example O and 100 mL of THF. Purification by silica gel chromatography, eluting with EtOAc:hexane (25:75 to 50:50) gave the title compound. 1H NMR (CDCl3) δ 0.0 (s, 6 H), 0.81 (s, 9 H), 2.17 (m, 2 H), 2.42 (m, 1 H), 2.63 (m, 1 H), 2.85 (dd, 2 H), 3.22 (dd, 2 H), 3.86-3.96 (m, 4 H), 6.80-7.19 (m, 9 H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][NH2:6].Cl[C:12]1[C:13]2[CH:26]=[C:25]([CH3:27])[S:24][C:14]=2[N:15]=[C:16]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:17]=1>>[N:21]1[CH:20]=[CH:19][C:18]([C:16]2[N:17]=[C:12]([NH:6][CH2:5][C:4]3[CH:7]=[CH:8][C:9]([Cl:10])=[C:2]([Cl:1])[CH:3]=3)[C:13]3[CH:26]=[C:25]([CH3:27])[S:24][C:14]=3[N:15]=2)=[CH:23][CH:22]=1
Reactant: NCc1ccc(Cl)c(Cl)c1
Reactant: Cc1cc2c(Cl)nc(-c3ccncc3)nc2s1
Product: Cc1cc2c(NCc3ccc(Cl)c(Cl)c3)nc(-c3ccncc3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of 3,4-dichlorobenzylamine with 4-chloro-2-(pyridin-4-yl)-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-(pyridin-4-yl)-4-(3,4-dichlorobenzylamino)-6-methyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH2:14][C:15]3[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=3)=[CH:10][C:9]=2[CH3:22])=[O:7])=[CH:4][CH:3]=1.Cl[CH2:26][CH2:27][S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([NH:19][S:28]([CH:27]=[CH2:26])(=[O:30])=[O:29])=[CH:20][CH:21]=3)=[CH:10][C:9]=2[CH3:22])=[O:7])=[CH:23][CH:24]=1
Reactant: Cc1cc(Cc2ccc(N)cc2)n(C)c1C(=O)c1ccc(Cl)cc1
Reactant: O=S(=O)(Cl)CCCl
Solvent: c1ccncc1
Product: C=CS(=O)(=O)Nc1ccc(Cc2cc(C)c(C(=O)c3ccc(Cl)cc3)n2C)cc1
Reaction time: 1.5 h
Yield: 92.5 %

Procedure:
4-[5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-ylmethyl]aniline (1.1 g, 3.25 mmol) was dissolved in pyridine (16.5 ml) and 2-chloroethanesulfonyl chloride (1.02 ml, 9.74 mmol) was added to the solution. The mixture was stirred for 1.5 h and then concentrated to dryness. The residue was filtered through a pad of silica gel (ethyl acetate) to give N-{4-[5-(4-chloro-benzoyl)-1,4-dimethyl-1H-pyrrol-2-ylmethyl]phenyl}ethenesulfonamide, (1.29 g, 93%) as a solid.
Reaction SMILES: [CH2:1]([C:3]1[NH:7][C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:5][CH:4]=1)[CH3:2].[Cl:13]C1C=C(C(OCC)=O)NC=1C>>[Cl:13][C:4]1[CH:5]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[NH:7][C:3]=1[CH2:1][CH3:2]
Reactant: CCOC(=O)c1ccc(CC)[nH]1
Reactant: CCOC(=O)c1cc(Cl)c(C)[nH]1
Product: CCOC(=O)c1cc(Cl)c(CC)[nH]1

Procedure:
Title compound was synthesized from ethyl 5-ethyl-1H-pyrrole-2-carboxylate (Intermediate 12) by an analogous method to Intermediate 9.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][Cl:5].C(=O)([O-])[O-].[K+].[K+].[I:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1>CC(C)=O>[Cl:5][CH2:4][CH2:3][CH2:2][O:19][C:16]1[CH:17]=[CH:18][C:13]([I:12])=[CH:14][CH:15]=1
Reactant: ClCCCBr
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: ClCCCOc1ccc(I)cc1
Temperature: 25 °C
Yield: 111.3 %

Procedure:
1-Bromo-3-chloropropane (21.4 g, 136 mmol) and potassium carbonate (30 g, 217 mmol) were added to an acetone (300 mL) solution of 4-iodophenol (20 g, 90.9 mmol), and stirred under reflux for 20 hours. The reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure to obtain the entitled compound (30 g, 100%).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:12]([S:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60][OH:61])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>C(Cl)Cl>[C:12]([S:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH2:59][CH2:60][O:61][S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: OCCOCCOCCOCCOCCOCCOCCCCCCCCCCCSC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCOCCOCCOCCOCCOCCOCCCCCCCCCCCSC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
p-Toluenesulfonyl chloride (900 mg, 4.7 mmol) was added to a solution of alcohol 4 (910 mg, 1.28 mmol) dissolved in 12 mL of CH2Cl2 and 2 mL of pyridine at 0° C. The solution was warmed to room temperature and stirred for 16 hours. The reaction mixture was rinsed with brine (2×30 mL) and H20 (2×30 mL), and then the organics were dried over MgSO4. After the solvent was evaporated, the crude residue was purified by flash chromatography (gradient, 1:1 hexanes/EtOAc to EtOAc) to afford 1.01 g (91%) of pure 5. 1H NMR (CDCl3, 400 MHz) d 7.79 (d, J=8.0 Hz, 2 H), 7.40 (d, J=7.8 Hz, 6 H), 7.33 (d, J=8.0 Hz, 2 H), 7.26 (t, J=7.8 Hz, 6 H), 7.19 (t, J=7.8 Hz, 3 H), 4.15 (t, J=4.8 Hz, 2 H), 3.67 (t, J=5.2 Hz, 2 H), 3.64-3.54 (br m, 20 H), 3.43 (t, J=6.8 Hz, 2 H), 2.45 (s, 3 H), 2.12 (t, J=7.2 Hz, 2 H), 1.56 (m, 2 H), 1.42-0.90 (br, 16 H).