Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])CCC.[F:19][C:20]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=1[CH2:22]Br>O1CCCC1>[CH3:10][O:9][C:6]1[C@@H:7]([CH2:22][C:21]2[CH:24]=[CH:25][C:26]([C:28]([F:29])([F:31])[F:30])=[CH:27][C:20]=2[F:19])[N:8]=[C:3]([O:2][CH3:1])[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=1
Reactant: COC1=N[C@@H](C(C)C)C(OC)=NC1
Reactant: Fc1cc(C(F)(F)F)ccc1CBr
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COC1=N[C@H](Cc2ccc(C(F)(F)F)cc2F)C(OC)=N[C@H]1C(C)C
Reaction time: 0.33 h

Procedure:
To a solution of 3.32 g (18 mmol) of commercially available (2S)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at −70° C. was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4-trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5% ethyl acetate in hexanes) afforded 5.5 g of the title compound. 1H NMR (500 MHz, CDCl3) δ 7.33-7.25 (m, 3H), 4.35-4.31 (m, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.60 (t, 1H, J=3.4 Hz), 3.33 (dd, 1H, J=4.6, 13.5 Hz), 3.03 (dd, 1H, J=7, 13.5 Hz), 2.25-2.15 (m, 1H), 1.0 (d, 3H, J=7 Hz), 0.66 (d, 3H, J=7 Hz).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[CH2:7][NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)(=[O:11])=[O:10])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:32][CH:33]=[C:34]([CH3:36])[CH3:35]>O1CCCC1.CN(C)C=O>[C:1]([O:5][C:6](=[O:20])[CH2:7][N:8]([S:9]([C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)(=[O:11])=[O:10])[CH2:32][CH:33]=[C:34]([CH3:36])[CH3:35])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)=CCBr
Reactant: COc1ccc(S(=O)(=O)NCC(=O)OC(C)(C)C)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)N(CC=C(C)C)CC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of (4-methoxybenzen sulfonylamino) acetic acid t-butyl ester (3.0 grams, 10 mmol) in tetrahydrofuran-dimethylformamide (mL, ca. 3:1) at 0° C. is added sodium bis(trimethylsilyl)amide (10.0 mL 1.0 M solution in tetrahydrofuran). After 10 minutes, 4-bromo-2-methyl-2-butene (1.27 μL, 11.0 mmol) is added. The mixture is warmed to room temperature, stirred for 1 hour and quenched with saturated ammonium chloride solution. The mixture is extracted with ethyl acetate and the combined extracts are dried (sodium sulfate), filtered and concentrated. The crude product is purified by silica gel chromatography (elution with 1:1 ethyl acetate-hexanes) to provide [(4-methoxybenzenesulfonyl)-(3-methyl-but-2-enyl)-amino]-acetic acid t-butyl ester.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[CH3:8].[CH3:10][O:11][C:12]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:13]=1[CH2:14][NH2:15]>CC(O)C>[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:15][CH2:14][C:13]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:12]=2[O:11][CH3:10])=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1cc(Cl)nnc1Cl
Reactant: COc1ccc(CN)c(OC)c1
Solvent: CC(C)O
Product: COc1ccc(CNc2cc(C)c(Cl)nn2)c(OC)c1
Temperature: 100 °C
Yield: 28 %

Procedure:
A mixture of 3,6-dichloro-4-methylpyridazine (1.35 g, 8.28 mmol) and 2,4-dimethoxybenzylamine (11.1 g, 66.3 mmol) in i-PrOH (5 ml) was heated in a microwave at 100° C. for 50 min. (30+20 min.). The mixture was concentrated and the residue was subjected to ISCO (120 g column, hexane 5 min., 0-55% EtOAc in hexane over 90 min. to give (6-chloro-5-methyl-pyridazin-3-yl)-(2,4-dimethoxy-benzyl)-amine (680 mg) plus the 6-methyl analog (320 mg).
Reaction SMILES: [C:1]1([C:7]2[N:8]([S:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)(=[O:31])=[O:30])[C:9]3[C:14]([CH:15]=2)=[C:13]([N:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)[CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:38]>C(Cl)Cl.CCOCC>[ClH:38].[C:1]1([C:7]2[N:8]([S:29]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)(=[O:30])=[O:31])[C:9]3[C:14]([CH:15]=2)=[C:13]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:12]=[CH:11][CH:10]=3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc3c2cc(-c2ccccc2)n3S(=O)(=O)c2ccccc2)CC1
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Product: O=S(=O)(c1ccccc1)n1c(-c2ccccc2)cc2c(N3CCNCC3)cccc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
tert-Butyl 4-[2-phenyl-1-(phenylsulfonyl)-1H-indol-4-yl]-1-piperazinecarboxylate (30 mg, 0.058 mmol) was dissolved in CH2Cl2 (1 mL) followed by addition of HCl in ether (1 mL). The reaction was shaken for 2 h at room temperature. The resulting precipitate was filtered off and washed with ether giving 20 mg of the desired compound (80%). 1H NMR (270 MHz, DMSO-d6) δ 9.02 (br, 1H), 7.90-7.80 (m, 3H), 7.75-7.55 (m, 3H), 7.32 (s, 1H), 7.22 (t, J=8 Hz, 1H), 6.79 (d, J=8 Hz, 1H), 3.35-310 (m, 8H). MS (ESI+) for m/z 418 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:11]([F:12])=[C:10]2[C:5]([C:6](=[O:19])[C:7]([C:16]([OH:18])=[O:17])=[C:8]3[S:15][CH2:14][CH2:13][N:9]32)=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>N1C=CC=CC=1>[F:12][C:11]1[C:2]([N:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)=[CH:3][CH:4]=[C:5]2[C:10]=1[N:9]1[CH2:13][CH2:14][S:15][C:8]1=[C:7]([C:16]([OH:18])=[O:17])[C:6]2=[O:19]
Reactant: O=C(O)c1c2n(c3c(F)c(Cl)ccc3c1=O)CCS2
Reactant: CN1CCNCC1
Solvent: c1ccncc1
Product: CN1CCN(c2ccc3c(=O)c(C(=O)O)c4n(c3c2F)CCS4)CC1
Yield: 33 %

Procedure:
8-Chloro-9-fluoro-5oxo-1,2-dihydro-5H-thiazolo(3,2-a)-quinoline-4-carboxylic acid (0.8 gram, 2.7 mmol) was dissolved in 5 ml of pyridine, then 2.7 grams (27 mmol) of N-methylpiperazine was added thereto, and the mixture was heated to reflux for forty eight hours. The content was concentrated under reduced pressure, water was added to the residue, and the insoluble matter was collected by filtration, washed with water, dried and recrystallized from dimethyl formamide to give 324 mg (42.0 percent) of the title compound, melting point 265° to 266° C. (decomposition). Elementary analyisis calculated as C17H18FN3O3S: C 56.19, H 4.99, N 11.56; Found: C 56.23, H 4.96, N 11.56.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][C:11]([OH:13])=O)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].C1N=CN(C(N2C=NC=C2)=O)C=1.C(N(CC)CC)C.Cl.[NH:34]1[CH2:37][CH:36]([OH:38])[CH2:35]1>C1COCC1>[OH:38][CH:36]1[CH2:37][N:34]([C:11](=[O:13])[CH2:10][C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:35]1
Reactant: OC1CNC1
Reactant: O=C(O)Cc1cccc([N+](=O)[O-])c1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Cc1cccc([N+](=O)[O-])c1)N1CC(O)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 78.2 %

Procedure:
THF (30 mL) was added to a mixture of 2-(3-Nitrophenyl)acetic acid (0.5 g, 2.76 mmol), CDI (0.671 g, 4.14 mmol), the mixture was stirred for 2 hrs at 0° C. followed by addition of triethylamine (1.2154 ml, 8.28 mmol) and azetidin-3-ol hydrochloride (0.756 g, 6.90 mmol). The reaction mixture was stirred for 12 hrs at room temperature and then concentrated under vacuum. The crude residue was purified by column chromatography using 0-50% ethyl acetate in hexanes as eluent to afford the title product (0.51 g).
Reaction SMILES: C[O:2][C:3](=[O:28])/[C:4](/[C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([C:23]([F:26])([F:25])[F:24])=[N:21][N:20]=[N:19]2)=[C:14]([Cl:27])[CH:13]=1)=[CH:5]/[CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Na+]>C(O)C>[Cl:27][C:14]1[CH:13]=[C:12](/[C:4](=[CH:5]\[CH:6]2[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)/[C:3]([OH:28])=[O:2])[CH:17]=[CH:16][C:15]=1[N:18]1[C:22]([C:23]([F:26])([F:24])[F:25])=[N:21][N:20]=[N:19]1
Reactant: COC(=O)/C(=C/C1CCCCC1)c1ccc(-n2nnnc2C(F)(F)F)c(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)/C(=C/C1CCCCC1)c1ccc(-n2nnnc2C(F)(F)F)c(Cl)c1
Temperature: 47.5 °C
Yield: 75.6 %

Procedure:
A solution of (E)-2-[3-chloro-4-(5-trifluoromethyl-tetrazol-1-yl)-phenyl]-3-cyclohexyl-acrylic acid methyl ester (833 mg, 2 mmol) in ethanol (10 mL) was treated with a 1N aqueous sodium hydroxide solution (4 mL). The solution was heated at 45-50° C. for 15 h, at which time, thin layer chromatography analysis of the mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo to remove ethanol, and the residue was diluted with water (20 mL) and extracted with diethyl ether (1×50 mL) to remove any neutral impurities. The aqueous layer was acidified with a 1N aqueous hydrochloric acid solution. The resulting acid was extracted into ethyl acetate (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford (E)-2-[3-chloro-4-(5-trifluoromethyl-tetrazol-1-yl)-phenyl]-3-cyclohexyl-acrylic acid (606 mg, 75%) as a brown solid: FAB-HRMS m/e calcd for C17H16ClF3N4O2 (M+H)+ 401.0992, found 401.0987.
Reaction SMILES: [CH2:1]([N:3]([CH2:22][CH3:23])[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][C:9]2[NH:12][C:13]([CH:19]=O)=[C:14]([C:15]([F:18])([F:17])[F:16])[C:8]=2[C:7]1=[O:21])[CH3:2].[Cl:24][C:25]1[CH:26]=[C:27]([NH:32][C:33]2[C:34]3[CH2:41][C:40](=[O:42])[NH:39][C:35]=3[N:36]=[CH:37][N:38]=2)[CH:28]=[CH:29][C:30]=1[F:31]>>[Cl:24][C:25]1[CH:26]=[C:27]([NH:32][C:33]2[C:34]3[C:41](=[CH:19][C:13]4[NH:12][C:9]5[CH2:10][CH2:11][N:6]([CH2:5][CH2:4][N:3]([CH2:22][CH3:23])[CH2:1][CH3:2])[C:7](=[O:21])[C:8]=5[C:14]=4[C:15]([F:17])([F:18])[F:16])[C:40](=[O:42])[NH:39][C:35]=3[N:36]=[CH:37][N:38]=2)[CH:28]=[CH:29][C:30]=1[F:31]
Reactant: O=C1Cc2c(ncnc2Nc2ccc(F)c(Cl)c2)N1
Reactant: CCN(CC)CCN1CCc2[nH]c(C=O)c(C(F)(F)F)c2C1=O
Product: CCN(CC)CCN1CCc2[nH]c(C=C3C(=O)Nc4ncnc(Nc5ccc(F)c(Cl)c5)c43)c(C(F)(F)F)c2C1=O
Yield: 48.5 %

Procedure:
The title compound was prepared under the same conditions as described in Example 123 with 5-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(3-chloro-4-fluoro-phenylamino)-5,7-dihydro-pyrrolo[2,3-d]-pyrimidin-6-one as starting materials to give 4-(3-chloro-4-fluoro-phenylamino)-5-[5-(2-diethylamino-ethyl)-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-ylmethylene]-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one (43 mg, 48.5%) as a yellow solid.
Reaction SMILES: [CH2:1]1[CH:9]2[N:4]([CH2:5][CH2:6][CH:7]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][N:17]=4)[NH:12][CH:11]=3)[CH2:8]2)[CH2:3][CH2:2]1.[C:19]1([S:29](Cl)(=[O:31])=[O:30])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1>C1COCC1>[CH2:1]1[CH:9]2[N:4]([CH2:5][CH2:6][CH:7]([C:10]3[C:14]4[C:13](=[CH:18][N:17]=[CH:16][CH:15]=4)[N:12]([S:29]([C:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:22]=[CH:21][CH:20]=4)(=[O:31])=[O:30])[CH:11]=3)[CH2:8]2)[CH2:3][CH2:2]1
Reactant: c1cnc2c(C3CCN4CCCC4C3)c[nH]c2c1
Reactant: O=S(=O)(Cl)c1cccc2ccccc12
Solvent: C1CCOC1
Product: O=S(=O)(c1cccc2ccccc12)n1cc(C2CCN3CCCC3C2)c2ccncc21

Procedure:
from 3-(octahydro-7-indolizinyl)-1-H-4-azaindole (more polar isomer) (12 mg, 0.05 mmol), 1-naphthalenesulfonyl chloride (20.9 mg, 0.1 mmol) and 1M NaN((TMS)2 (100 μL, 0.10 mmol) in THF (1 mL) at RT.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[Br-:12].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>O1CCCC1>[Br:12][CH2:10][C:9]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[Br:1])=[O:11]
Reactant: CC(=O)c1ccc(F)cc1Br
Reactant: [Br-]
Agent: C[N+](C)(C)c1ccccc1
Solvent: C1CCOC1
Product: O=C(CBr)c1ccc(F)cc1Br
Temperature: 25 °C
Reaction time: 16 h
Yield: 62.8 %

Procedure:
To 1-(2-Bromo-4-fluoro-phenyl)-ethanone (2.5 g, 11.52 mmol) in anhydrous tetrahydrofuran (53 mL) under argon was added phenyltrimethylammonium tribromide (4.33 g, 11.52 mmol, 1.0 eq) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h, concentrated, and re-dissolved in ethyl acetate. The organic layer was washed with water (2×150 mL) and brine (1×100 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification using MPLC chromatography (Biotage) gave 2.14 g (63%) of 2-bromo-1-(2-bromo-4-fluoro-phenyl)-ethanone as a clear oil. 1H-NMR (CD2Cl2) δ 7.57 (dd, J=9.6 Hz, 1H), 7.44 (dd, J=8, 2 Hz, 1H), 7.21 (m, 7.21-7.14, 1H), 4.51 (s, 2H); TLC Rf=0.38, 15% ethyl acetate-hexanes.
Reaction SMILES: [S:1]([NH2:5])([NH2:4])(=[O:3])=[O:2].[O:6]=[S:7]1(=[O:14])[CH2:11][CH2:10][CH:9]([CH2:12]N)[CH2:8]1>O>[O:6]=[S:7]1(=[O:14])[CH2:11][CH2:10][CH:9]([CH2:12][NH:4][S:1](=[O:3])(=[O:2])[NH2:5])[CH2:8]1
Reactant: NCC1CCS(=O)(=O)C1
Reactant: NS(N)(=O)=O
Solvent: O
Product: NS(=O)(=O)NCC1CCS(=O)(=O)C1
Temperature: 25 °C

Procedure:
Sulfamide (2.4 mmol) was dissolved in H2O (10 mL), added (1,1-dioxothiolan-3-yl)methanamine (2 mmol) and stirred at reflux for 16 h. The obtained reaction mixture was cooled to rt and freezedried affording the title compound as an oil. Used without further purification.
Reaction SMILES: [OH-].[NH4+:2].[F:3][C:4]1[CH:9]=[C:8]([Br:10])[C:7]([F:11])=[CH:6][C:5]=1[S:12](Cl)(=[O:14])=[O:13].O>O1CCCC1>[Br:10][C:8]1[C:7]([F:11])=[CH:6][C:5]([S:12]([NH2:2])(=[O:14])=[O:13])=[C:4]([F:3])[CH:9]=1
Reactant: [NH4+]
Reactant: O=S(=O)(Cl)c1cc(F)c(Br)cc1F
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: NS(=O)(=O)c1cc(F)c(Br)cc1F
Reaction time: 0.17 h

Procedure:
Ammonium hydroxide (5 ml) was added to a solution of 2,5-difluoro-4-bromophenylsulfonyl chloride (4.3 g) in tetrahydrofuran (20 ml) at room temperature (CARE:exotherm) and stirred for 10 min. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the residue triturated with 20% diethyl ether in isohexane to give the sub-title compound as a solid (4.3 g).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[N:5][C:6]2[C:7](=[C:9]([NH2:14])[N:10]=[C:11]([NH2:13])[N:12]=2)[N:8]=1.[CH2:15]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(O)C>[CH2:15]([N:22]1[CH2:27][CH2:26][N:25]([CH2:2][C:3]2[N:4]=[N:5][C:6]3[C:7](=[C:9]([NH2:14])[N:10]=[C:11]([NH2:13])[N:12]=3)[N:8]=2)[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: c1ccc(CN2CCNCC2)cc1
Reactant: Nc1nc(N)c2nc(CCl)nnc2n1
Solvent: CCO
Product: Nc1nc(N)c2nc(CN3CCN(Cc4ccccc4)CC3)nnc2n1
Temperature: 90 °C

Procedure:
A mixture of 3-Chloromethyl-pyrimido[5,4-e][1,2,4]triazine-5,7-diamine 3 (48 mg; 0.23 mmol) and N-Benzylpiperazine (0.12 mL) in ethanol (0.1 mL) were heated to 90° C. in a sealed tube for 2 h. The mixture was then allowed to cool to room temperature and concentrated in vacuo. The crude product was purified by reverse phase HPLC (Rainin C18, 0% CH3CN to 50% CH3CN gradient, CH3CN/H2O, 0.1% TFA) and the bright yellow fractions containing the product were lyophilized after removal of CH3CN in vacuo to give 26 mg of yellow colored 3-(4-Benzyl-piperazin-1-ylmethyl)-pyrimido[5,4-e][1,2,4]triazine-5,7-diamine as the trifluoroacetate salt.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:12])=[CH:10][CH:11]=1.[CH2:13]([SiH:16]([Cl:18])[Cl:17])[CH:14]=[CH2:15]>>[CH3:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][C:7]=1[CH:14]([CH3:15])[CH2:13][SiH:16]([Cl:18])[Cl:17]
Reactant: C=CC[SiH](Cl)Cl
Reactant: Cc1ccc(C)cc1
Agent: [Al+3]
Agent: [Cl-]
Product: Cc1ccc(C)c(C(C)C[SiH](Cl)Cl)c1
Yield: 52.6 %

Procedure:
In the same apparatus and procedures as Example 1, 0.9 g (0.007 mol) of aluminum chloride and 37 g (0.349 mol) of p-xylene were reacted with 10 g (0.07 mol) of allyldichlorosilane at 0° C. for 1.5 hrs. Vacuum distillation of the solution gave 9.1 g (81%) of 3-(2,5-dimethylphenyl)-1,1-dichloro-1-silabutane (boiling point: 86°-9° C./0.6 mmHg).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[NH:9][CH2:8][CH2:7]2.[CH3:16][N:17]([CH3:23])[C@@H:18]([C:20](O)=[O:21])[CH3:19].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:16][N:17]([CH3:23])[C@H:18]([CH3:19])[C:20]([N:9]1[C:10]2[C:6](=[CH:5][C:4]([O:3][CH3:2])=[C:12]([N+:13]([O-:15])=[O:14])[CH:11]=2)[CH2:7][CH2:8]1)=[O:21]
Reactant: C[C@H](C(=O)O)N(C)C
Reactant: COc1cc2c(cc1[N+](=O)[O-])NCC2
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc2c(cc1[N+](=O)[O-])N(C(=O)[C@@H](C)N(C)C)CC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.5 %

Procedure:
To a solution of 5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole hydrogen chloride (2 g, 8.67 mmol) in N,N-dimethylformamide (100 mL) was added N,N-dimethyl-D-alanine (1.524 g, 13.01 mmol), PyBOP (13.54 g, 26.0 mmol), and DIPEA (15.14 mL, 87 mmol). After stirring overnight at rt, the solvent was removed and the residue was suspended in dichloromethane (150 mL), washed with water (100 mL), concentrated on the rotovap, and purified by column chromatography (DCM to 5% MeOH/DCM) to provide 1-[(2R)-N,N-dimethyl-1-[5-(methyloxy)-6-nitro-2,3-dihydro-1H-indol-1-yl]-1-oxo-2-propanamine (2.2 g, 86%). ESIMS (M+H)+=294.
Reaction SMILES: [N:1]([Sn](C)(C)C)=[N+:2]=[N-:3].[C:8]1([C:14]2([C:21]3[CH:28]=[C:27]([O:29][CH2:30][C:31]4[CH:40]=[CH:39][C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[N:32]=4)[CH:26]=[CH:25][C:22]=3[C:23]#[N:24])[CH2:19][CH:18]3[CH2:20][CH:15]2[CH2:16][CH2:17]3)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1(C)C=CC=CC=1>[C:8]1([C:14]2([C:21]3[CH:28]=[C:27]([CH:26]=[CH:25][C:22]=3[C:23]3[NH:24][N:3]=[N:2][N:1]=3)[O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)[CH2:19][CH:18]3[CH2:20][CH:15]2[CH2:16][CH2:17]3)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: C[Sn](C)(C)N=[N+]=[N-]
Reactant: N#Cc1ccc(OCc2ccc3ccccc3n2)cc1C1(c2ccccc2)CC2CCC1C2
Solvent: Cc1ccccc1
Product: c1ccc(C2(c3cc(OCc4ccc5ccccc5n4)ccc3-c3nnn[nH]3)CC3CCC2C3)cc1
Temperature: 140 °C
Reaction time: 72 h

Procedure:
Azidotrimethyltin (82.0 mg, 0.40 mmol) was added to a stirred solution of 6a (40.0 mg, 0.09 mmol) in toluene (0.6 mL) at room temperature and the resulting mixture heated to 140° C. After 72 h, the reaction mixture was cooled to room temperature, and the volatiles were removed in vacuo. The residue was taken up in cold hydrogen chloride/MeOH (1 mL; saturated solution) and stirred for 20 min at room temperature. The reaction mixture was concentrated in vacuo, and the crude residue was purified by flash chromatography on silica gel (gradient elution, 0-10% methanol/methylene chloride as eluent) to furnish the title compound as an off-white foam. Rf: 0.15 (1:2 hexane:EtOAc). m/z (ES) 474 (MH)+. 1H NMR (500 M, CDCl3): δ 0.89-0.93 (m, 1H), 1.19-1.26 (m, 1H), 1.26-1.40 (m, 2H), 1.46-1.55 (m, 1H), 1.72 (br d, 1H), 1.88 (td, J=2.8, 13.6 Hz, 1H), 2.03 (dd, J=2.3, 13.7 Hz, 1H), 2.34 (br s, 1H), 3.01 (br d, J=3.6 Hz, 1H), 5.55 (s, 2H), 6.94 (dd, J=2.3, 8.4 Hz, 1H), 7.0-7.22 (m, 3H), 7.22-7.32 (m, 3H), 7.62-7.68 (m, 2H), 7.78-7.86 (m, 2H), 7.90-7.96 (m, 1H), 8.20 (m, 1H), 8.37 (m, 1H).
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:16])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.[CH3:17]N(C=O)C.[H-].[Na+].IC>O>[Br:1][C:2]1[C:3]([O:16][CH3:17])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:12])([CH3:13])[C:10]=2[CH:11]=1
Reactant: CC1(C)CCC(C)(C)c2cc(Br)c(O)cc21
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COc1cc2c(cc1Br)C(C)(C)CCC2(C)C

Procedure:
7 g (24.7 mmol) of 3-bromo-2-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene and 40 ml of DMF are introduced into a three-necked flask under a stream of nitrogen. 890 mg (29.6 mmol) of sodium hydride (80% in oil) are added portionwise and the mixture is stirred until the evolution of gas has ceased. 1.7 ml (27 mmol) of iodomethane are then added and the mixture is stirred at room temperature for one hour. The reaction medium is poured into water and extracted with ethyl ether, and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. 7.3 g (99%) of the expected product are collected in the form of an oil which crystallizes slowly. Melting point 77-8° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([Cl:15])=[C:4]([Cl:14])[C:5]([Cl:13])=[C:6]2[C:11](=[O:12])O[C:8](=[O:9])[C:7]=12.[CH:16]1[C:21]([NH2:22])=[CH:20][CH:19]=[C:18]([NH2:23])[CH:17]=1>CN1CCCC1=O>[C:18]1([N:23]2[C:8](=[O:9])[C:7]3=[C:2]([Cl:1])[C:3]([Cl:15])=[C:4]([Cl:14])[C:5]([Cl:13])=[C:6]3[C:11]2=[O:12])[CH:19]=[CH:20][C:21]([N:22]2[C:11](=[O:12])[C:6]3=[C:5]([Cl:13])[C:4]([Cl:14])=[C:3]([Cl:15])[C:2]([Cl:1])=[C:7]3[C:8]2=[O:9])=[CH:16][CH:17]=1
Reactant: Nc1ccc(N)cc1
Reactant: O=C1OC(=O)c2c(Cl)c(Cl)c(Cl)c(Cl)c21
Solvent: CN1CCCC1=O
Product: O=C1c2c(Cl)c(Cl)c(Cl)c(Cl)c2C(=O)N1c1ccc(N2C(=O)c3c(Cl)c(Cl)c(Cl)c(Cl)c3C2=O)cc1
Temperature: 200 °C
Yield: 52.9 %

Procedure:
In a 5 liter round-bottom flask equipped with a heating mantle, a stirrer, a thermometer, a condenser and a nitrogen purge, there were reacted 457.5 gms (1.6 mole) of tetrachlorophthalic anhydride and 86.5 gms (0.8 mole) of p-phenylenediamine in 2000 ml. of N-methyl-2-pyrrolidone (NMP), the reactants going into solution as the mixture was heated with stirring. At 170° C., precipitation began and continued as the temperature was raised to 200° C. where it was maintained for 90 minutes. The reaction mixture was then allowed to cool overnight. The cooled mixture was filtered and the yellow precipitate was recovered. The precipitate was washed with NMP, thoroughly stirred in acetone, filtered and washed with more acetone. The product was dried under vacuum at 150° C. for 16 hours. 272.7 gms (yield=53%) of an ivory-yellow material was obtained, having a melting point in excess of 500° C., with some sublimation at about 425° C. The IR spectrum had the characteristics of an imide with the absorption bands at 1710s and 1770w cm-1. The product was insoluble in water.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[NH2:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:16]1(=O)[CH2:20][CH2:19][C:18](=[O:21])[CH2:17]1.O>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[NH:10][C:16]2[CH2:20][CH2:19][C:18](=[O:21])[CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C1CCC(=O)C1
Reactant: COc1ccc(N)cc1OC1CCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: COc1ccc(NC2=CC(=O)CC2)cc1OC1CCCC1
Temperature: 25 °C
Yield: 80.4 %

Procedure:
1.04 g (5.02 mole) of 3-cyclopentyloxy-4-methoxyaniline, 0.51 g (5.02 mmole) of 1,3-cyclopentanedione, and 0.03 g of p-toluenesulfonic acid were dissolved in 30 ml of benzene and the solution was heated reflux in an apparatus fitted with a water separation tube for 3 hours, while azeotropically separating the water produced. After the reaction, the solution was cooled to room temperature, a yellow crystal was precipitated. The precipitated yellow crystal was collected by suction filtration, and the crystal was washed with diethyl ether, then dried to obtain the title compound 1.16 g (yield 80.4%) as a pale yellow crystal.