Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.Cl.Cl.[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][C@H:15]1[CH2:20][OH:21].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>C(OCC)(=O)C.O>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:16][C@H:15]1[CH2:20][OH:21]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CN1CCNC[C@H]1CO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: CN1CCN(c2ccc([N+](=O)[O-])cc2)C[C@H]1CO
Temperature: 120 °C
Reaction time: 3 h

Procedure:
A mixture of 1-fluoro-4-nitrobenzene (418 μL), [(2S)-1-methylpiperazin-2-yl]methanol dihydrochloride (0.8 g), potassium carbonate (2.45 g), and dimethylsulfoxide (8 mL) was stirred at 120° C. for 3 hours. To the reactant were added water and ethyl acetate, followed by liquid separation. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH2 type: eluent; ethyl acetate) to obtain [(2S)-1-methyl-4-(4-nitrophenyl)piperazin-2-yl]methanol (590 mg) as a yellow solid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][N:12]=2)[CH2:3][CH2:2]1.[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[CH3:26])[CH2:21]Br.N12CCCNC1=NCCC2>C(#N)C>[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[CH3:26])[CH2:21][N:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:14])[F:15])=[N:11][N:12]=2)[CH2:3][CH2:2]1
Reactant: Cc1ccc(CBr)cc1F
Reactant: FC(F)(F)c1nnc(NC2CCNCC2)s1
Agent: C1CN=C2NCCCN2C1
Solvent: CC#N
Product: Cc1ccc(CN2CCC(Nc3nnc(C(F)(F)F)s3)CC2)cc1F
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 45.4 %

Procedure:
A mixture of piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D4) (0.025 g, 0.1 mmol), 3-fluoro-4-methylbenzyl bromide (0.012 ml, 0.11 mmol) and polymer supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (2.9 mmol/g) (0.102 g, 0.30 mmol) in acetonitrile (3 ml) was stirred at 80° C. for 30 min. After cooling to room temperature, the reaction mixture was filtered through an Isolute SCX-2 cartridge. The cartridge was then washed with methanol. The crude product was eluted with a 7M solution of ammonia in methanol. The solvent was evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 5% ammonia in methanol (7M)/dichloromethane) to yield E9 (0.017 g, 45%) as a solid. C16H18F4N4S requires 374. Found 375 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[CH:27]=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([N:11]2[CH2:12][CH2:13][N:14]([CH2:27][C:18]3[CH:19]=[CH:20][C:21]4[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:17]=3)[CH2:15][CH2:16]2)=[O:10])=[CH:6][CH:7]=1
Reactant: O=Cc1ccc2ccccc2c1
Reactant: O=C(Nc1ccc(F)cc1)N1CCNCC1
Product: O=C(Nc1ccc(F)cc1)N1CCN(Cc2ccc3ccccc3c2)CC1

Procedure:
The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and 2-naphthalenecarbaldehyde. 1H NMR (400 MHz, CDCl3): 7.85-7.80 (m, 3H), 7.74 (s, 1H), 7.52-7.45 (m, 3H), 7.30-7.25 (m, 2H), 6.98-6.92 (m, 2H), 6.36 (s, 1H), 3.69 (s, 2H), 3.49 (t, J=5.1 Hz, 4H), 2.51 (t, J=5.1 Hz, 4H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.Br[CH2:10][CH:11]([CH3:13])[CH3:12].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:4][N:3]=1
Reactant: CC(C)CBr
Reactant: Oc1cnc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)COc1cnc(Cl)nc1
Temperature: 80 °C

Procedure:
0.80 mg (6.13 mmol) 2-chloro-5-hydroxypyrimidine, 1.26 g (9.19 mmol) 1-bromo-2-methylpropane and 1.69 g (12.26 mmol) K2CO3 are added to 10 mL DMF and stirred at 80° C. over night. Afterwards the reaction is quenched by the addition of water and extracted with EtOAc. The org. layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo.
Reaction SMILES: [CH2:1]([Zn]CC)C.FC(F)(F)C(O)=O.ICI.[Si:16]([O:23][C@H:24]1[CH2:33][C:32]([CH3:35])([CH3:34])[CH2:31][C:30]2[N:29]=[C:28]([C:36]([CH3:38])=[CH2:37])[C:27]3[C@@H:39]([C:47]4[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=4)[O:40][C:41]4([CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:26]=3[C:25]1=2)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>ClCCl>[Si:16]([O:23][C@H:24]1[CH2:33][C:32]([CH3:35])([CH3:34])[CH2:31][C:30]2[N:29]=[C:28]([C:36]3([CH3:1])[CH2:38][CH2:37]3)[C:27]3[C@@H:39]([C:47]4[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:54])[F:55])=[CH:49][CH:48]=4)[O:40][C:41]4([CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:26]=3[C:25]1=2)([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17]
Reactant: CC[Zn]CC
Reactant: C=C(C)c1nc2c(c3c1[C@@H](c1ccc(C(F)(F)F)cc1)OC31CCOCC1)[C@@H](O[Si](C)(C)C(C)(C)C)CC(C)(C)C2
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: ICI
Product: CC1(C)Cc2nc(C3(C)CC3)c3c(c2[C@@H](O[Si](C)(C)C(C)(C)C)C1)C1(CCOCC1)O[C@@H]3c1ccc(C(F)(F)F)cc1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
536 μl Diethylzinc (1 M in n-hexane) are dissolved in 5 ml dichloromethane, cooled to 0° C. and treated dropwise with a solution of 41 μl trifluoroacetic acid in 5 ml dichloromethane. The mixture is stirred for 20 minutes and then 41 μl diiodomethane in 2.5 ml dichloromethane are added dropwise. After stirring for further 20 minutes a solution of 150 mg (3R,9S)-9-(tert-butyldimethylsilyloxy)-7,7-dimethyl-4-(prop-1-en-2-yl)-3-(4-(trifluoromethyl)phenyl)-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran] in 2.5 ml dichloromethane are added dropwise. The mixture is then allowed to warm to room temperature and is stirred for 4 hours. Then it is partitioned between saturated solution of sodium bicarbonate in water and dichloromethane. The aqueous phase is twice extracted with dichloromethane. The combined organic phases are dried with sodium sulphate and the solvents are evaporated in vacuo. The residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 85:15).
Reaction SMILES: C[O:2][C:3]1[C:4]([CH3:41])=[C:5]([C:32]([O:39]C)=[C:33]([O:37][CH3:38])[C:34]=1[O:35][CH3:36])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=[C:11]([CH:25]=1)[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[O:13].O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(#N)C.O>[CH3:36][O:35][C:34]1[C:3](=[O:2])[C:4]([CH3:41])=[C:5]([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[C:11]([CH:25]=2)[C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:19][CH:20]=2)=[O:13])[C:32](=[O:39])[C:33]=1[O:37][CH3:38]
Reactant: COc1c(C)c(Cc2ccc(-c3cccnc3)c(C(=O)Nc3ccc(C(F)(F)F)cc3)c2)c(OC)c(OC)c1OC
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: COC1=C(OC)C(=O)C(Cc2ccc(-c3cccnc3)c(C(=O)Nc3ccc(C(F)(F)F)cc3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 31.6 %

Procedure:
N-[5-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-(3-pyridyl)benzoyl]-4-trifluoromethylaniline (60 mg, 0.1060 mmol) was dissolved in a mixed solvent of acetonitrile (9 ml) and water (3 ml), then CAN (228 mg, 0.4237 mmol) was added thereto at room temperature and the mixture was stirred for 3 hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried and the solvent was evaporated therefrom. The residue was purified by preparative thin layer chromatography (methylene chloride:methanol=95:5) to give the title compound (18 mg, 0.0335 mmol, 32%).
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21](O)=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][N:26]1[CH2:35][CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([NH2:36])[CH:32]=2)[CH2:27]1>>[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21]([NH:36][C:31]4[CH:32]=[C:33]5[C:28](=[CH:29][CH:30]=4)[CH2:27][N:26]([CH3:25])[CH2:35][CH2:34]5)=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN1CCc2cc(N)ccc2C1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(-c2ccc3cnc(O)nn23)c1
Product: CN1CCc2cc(Nc3ncc4ccc(-c5cccc(S(=O)(=O)NC(C)(C)C)c5)n4n3)ccc2C1
Yield: 52.2 %

Procedure:
N-tert-Butyl-3-(2-hydroxy-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide (0.109 g, 0.316 mmol) and 2-Methyl-1,2,3,4-tetrahydro-isoquinolin-6-ylamine (0.064 g, 0.39 mmol) were reacted in an analogous manner to Example 908D at rt for 16 h. The reaction mixture was concentrated, taken up in EtoAc, and washed with water. The organic layer was dried over MgSO4, filtered, and concentrated. The resulting solid was purified by ISCO silica gel chromatography (0-10% MeOH in CH2Cl2) to afford title compound (81 mg, 52%). HPLC purity=96%, rt=2.654, LCMS=491.0 (M+H) 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.48 (s, 1H), 9.04 (s, 1H), 8.50 (d, J=7.9 Hz, 1H), 8.39 (s, 1H), 7.84 (d, J+7.4 Hz, 1H), 7.73 (dd, J=7.9 Hz, 7.9 Hz, 1H), 7.61 (s, 1H), 7.58 (s, 1H0, 7.48 (dd, J=8.3 Hz, 1.67 Hz, 1H), 7.18 (d, J=4.7 Hz, 1H), 7.03 (d, J=8.3 Hz, 1H), 7.00 (d, J=4.8 Hz, 1H), 3.67-3.61 (m, 2H), 2.85 (s, 3H), 2.80-2.70 (m, 2H), 2.48-2.42 (m, 2H), 1.11 (s, 9H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:11]=[CH:10][C:9]=2[N+:21]([O-])=O)[CH:5]=[CH:6][CH:7]=1.O.[Cl-].[NH4+]>C(O)C.ClCCl.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:19])([CH3:18])[CH3:20])[N:11]=[CH:10][C:9]=2[NH2:21])[CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)COCCn1ncc([N+](=O)[O-])c1-c1cccc(Br)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Solvent: ClCCl
Product: C[Si](C)(C)COCCn1ncc(N)c1-c1cccc(Br)c1
Temperature: 75 °C
Reaction time: 6 h
Yield: 60 %

Procedure:
To a solution of 5-(3-bromophenyl)-4-nitro-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazole (800 mg, 2.4 mmol) in 25 mL ethanol was added 50 mL of water, ammonium chloride (636 mg, 12 mmol), and iron powder (806 mg, 14 mmol). The reaction mixture was stirred at 75° C. for 6 hours. After cooling to room temperature, the reaction was diluted with dichloromethane and filtered through a celite pad, rinsing with more dichloromethane. The filtrate was added to 150 mL of saturated aqueous sodium bicarbonate and extracted twice with dichloromethane. The combined organic extracts were dried over magnesium sulfate and concentrated to yield 530 mg (71%) of 5-(3-bromophenyl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amine, which was carried forward without purification. LCMS (ESI) m+H=368.0.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1.C([Li])CCC.CN(C)CCN(C)C.C([O:27][B:28](OC(C)C)[O:29]C(C)C)(C)C.Cl>C(OCC)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[B:28]([OH:29])[OH:27]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: COc1cccc(OC)c1
Agent: CN(C)CCN(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Product: COc1cccc(OC)c1B(O)O
Temperature: -78 °C
Reaction time: 1.5 h

Procedure:
A solution of 1,3-dimethoxybenzene (33.2 g, 240 mmol) in hexanes (20 mL) at −20° C. was treated sequentially with n-butyllithium (100 mL of a 2.4M solution in hexanes, 240 mmol) and N,N,N′,N′-tetramethylethylenediamine (1.81 mL, 12 mmol), stirred for 1.5 hours, cooled to −78° C., treated with triisopropylborate (60.9 mL, 264 mmol) in diethyl ether (60 mL) over 1.5 hours with additional diethyl ether (150 mL) added to maintain stirring, stirred at 23° C. for 2 hours, poured into ice (150 mL) and 3M HCl (150 mL), and extracted with ethyl acetate. The extract was dried (Na2SO4), filtered, and concentrated, during which a white solid precipitated. The solid was collected by filtration and washed with hexanes to provide the desired compound, which used without further purification. MS (DCI/NH3) m/z 200 (M+NH4)+.
Reaction SMILES: Br[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=O.[CH2:15]([NH2:18])[CH2:16][NH2:17]>C(O)CCC>[N+:12]([C:11]1[C:2]2[NH:18][CH2:15][CH2:16][NH:17][C:4](=[O:6])[C:3]=2[CH:8]=[CH:9][CH:10]=1)([O-:14])=[O:13]
Reactant: NCCN
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1Br
Solvent: CCCCO
Product: O=C1NCCNc2c1cccc2[N+](=O)[O-]
Reaction time: 0.5 h

Procedure:
A mixture of 11.7 parts of methyl 2-bromo-3-nitrobenzoate, 8.1 parts of 1,2-ethanediamine mononohydrate and 40 parts of 1-butanol was stirred for ½ hour at reflux temperature. The reaction mixture was evaporated and the residue was diluted with 50 parts of water. The precipitate was filtered off and washed with water and 2-propanol. It was then recrystallized from 2-methoxyethanol, yielding 6.5 parts of 2,3,4,5-tetrahydro-9-nitro-1H-1,4-benzodiazepin-5-one; m.p. 191-195° C. (interm. 1).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([S:29]([CH:32]4[CH2:34][CH2:33]4)(=[O:31])=[O:30])[CH2:25][CH2:24]3)=[O:22])[N:8]2[CH2:11][CH2:12][O:13][Si](C(C)(C)C)(C)C)=[CH:4][C:3]=1[O:35][CH:36]1[CH2:41][CH2:40][N:39]([CH:42]([CH3:44])[CH3:43])[CH2:38][CH2:37]1.FC(F)(F)C(O)=O>ClCCl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([S:29]([CH:32]4[CH2:34][CH2:33]4)(=[O:30])=[O:31])[CH2:25][CH2:24]3)=[O:22])[N:8]2[CH2:11][CH2:12][OH:13])=[CH:4][C:3]=1[O:35][CH:36]1[CH2:37][CH2:38][N:39]([CH:42]([CH3:44])[CH3:43])[CH2:40][CH2:41]1
Reactant: CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO[Si](C)(C)C(C)(C)C)c3cc2Br)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)N1CCC(Oc2cc3cc(C(=O)N4CCN(S(=O)(=O)C5CC5)CC4)n(CCO)c3cc2Br)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99 %

Procedure:
A solution of 85 mg (0.12 mmol) [6-bromo-1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-cyclopropanesulfonyl-piperazin-1-yl)-methanone in 2 mL dichloromethane was cooled to 0° C. and 1.0 mL (1.49 g, 13.1 mmol) trifluoroacetic acid were added. The cooling bath was removed and after stirring for 1 h at room temperature the solution was evaporated to dryness. The residue was taken up in dichloromethane and extracted with 1M aqueous sodium hydroxide solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated to afford 71 mg (99%) of the title compound as colourless oil.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2.[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[N:14]1([CH2:2][CH2:3][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[NH:9][C:8](=[O:13])[CH2:7]3)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1
Reactant: C1COCCN1
Reactant: O=C1Cc2cc(CCCl)ccc2N1
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: O
Product: O=C1Cc2cc(CCN3CCOCC3)ccc2N1
Yield: 31 %

Procedure:
A solution of 5-(2-chloroethyl)-2-oxindole (2.3 g), morpholine (1.2 ml) and diisopropylethylamine (1.2 ml) in dimethylsulfoxide (10 ml) was heated overnight at 100° C. The mixture was cooled, poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried and evaporated. The residue was chromatographed (silica gel, 5% methanol in chloroform) to give 0.9 g (31%) of 5-(2-morpholin-4-yl-ethyl)-2-oxindole as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12](O)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(OC([CH:70]([NH2:77])[CH:71]1[CH2:76][CH2:75][CH2:74][NH:73][CH2:72]1)=O)(C)(C)C.FC(F)(F)C(O)=O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:73]1[CH2:74][CH2:75][CH2:76][CH:71]([CH2:70][NH2:77])[CH2:72]1)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: CC(C)(C)OC(=O)C(N)C1CCCNC1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2cc(C(=O)N3CCCC(CN)C3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 3-(tert.-butyloxycarbonyl-aminomethyl)-piperidine in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][P:11]([O-:15])[O:12][CH2:13][CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.C[Si](Cl)(C)C.Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>C(Cl)(Cl)Cl>[CH2:13]([O:12][P:11]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])([CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:15])[CH3:14]
Reactant: CCOP([O-])CCCCc1ccccc1
Reactant: CCOC(=O)CBr
Agent: C[Si](C)(C)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCOC(=O)CP(=O)(CCCCc1ccccc1)OCC
Temperature: 0 °C
Reaction time: 6 h

Procedure:
To a solution of 4-phenylbutyl phosphonous acid, ethyl ester (0.5 g, 0.0022 mole) in chloroform (10 ml) was added triethylamine (0.34 ml, 0.0024 mole) and the solution was cooled in an ice bath to 0° C. Trimethyl silyl chloride (0.31 ml, 0.0024 mole) was added to the above solution dropwise, followed by ethyl bromoacetate (0.27 ml, 0.0024 mole). The ice bath was removed and the mixture stirred at room temperature for 6 hours and poured into 50% aqueous HCl (30 ml) and crushed ice (20 g). After shaking the mixture in a separatory funnel, the chloroform layer was separated and the aqueous layer extracted with dichloromethane (2×50 ml). The combined organic phase was washed with brine, dried over anhydrous sodium sulfate and the solvents removed on a rotavap. The resulting yellow oil (0.6 g) was vacuum dried to get 0.58 (84%) of title compound. TLC, silica gel, acetone:hexane (1:1), Rf =0.28.
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].[CH3:5][C:6]1[C:12]([CH3:13])=[C:11]([OH:14])[CH:10]=[C:9]([C:15](=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:7]=1[OH:8].C(=O)([O-])[O-].[K+].[K+].C(C(C)=O)C>O>[CH2:1]([O:8][C:7]1[C:9]([C:15](=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:10][C:11]([OH:14])=[C:12]([CH3:13])[C:6]=1[CH3:5])[CH:2]=[CH2:3]
Reactant: C=CCBr
Reactant: CCCCCCCCCCCCCC(=O)c1cc(O)c(C)c(C)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCC(C)=O
Product: C=CCOc1c(C(=O)CCCCCCCCCCCCC)cc(O)c(C)c1C
Temperature: 30 °C
Reaction time: 9 h

Procedure:
43 g of allyl bromide were dropwise added with gentle boiling within 2 h to a mixture of 105 g of the ketone of step 1, 63 g of potassium carbonate and 1200 ml of methyl ethyl ketone. After 9 h of boiling the mixture was cooled to 30° C. and 200 ml of water were added. The aqueous layer was separated. Then the organic layer was shaken once with a 25% by weight sodium chloride solution and filtered off, whereupon the solvent was distilled. The residue was stirred into 1 l of methanol and filtered with suction.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.[H-].[Na+].[Si:16]([O:23][C@@H:24]1[C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@@H:26]([O:38][C:39]2[N:47]=[CH:46][N:45]=[C:44]3[C:40]=2[N:41]=[C:42](I)[N:43]3C2CCCCO2)[CH2:25]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>>[Si:16]([O:23][C@@H:24]1[C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33])[CH2:27][C@@H:26]([O:38][C:39]2[N:47]=[CH:46][N:45]=[C:44]3[C:40]=2[N:41]=[C:42]([S:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)[NH:43]3)[CH2:25]1)([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:17])[CH3:18]
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](Oc2ncnc3c2nc(I)n3C2CCCCO2)C[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: Cc1cccc(S)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cccc(Sc2nc3c(O[C@@H]4C[C@@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)C4)ncnc3[nH]2)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 82.1 %

Procedure:
To a solution of 3-methylbenzenethiol (0.55 mL, 0.0046 mol) in DMF (10 mL, 0.2 mol) was added sodium hydride (0.093 g, 0.0023 mol). The mixture was stirred at room temperature for 10 minutes and then 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-8-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (400 mg, 0.0006 mol) (Example 115, steps a-b) was added and the solution was heated at 150° C. for 8 hours. The reaction was cooled, quenched by addition of water and the mixture was extracted with ethyl acetate, washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 30% ethyl acetate/hexanes) to obtain 296 mg (80%) of the title compound.
Reaction SMILES: Cl.Cl.NCCNC1C=CC(C#N)=CN=1.C(OC(=O)[NH:21][CH2:22][CH2:23][NH:24][C:25]1[S:26][C:27]([C:31]#[N:32])=[C:28]([NH2:30])[N:29]=1)(C)(C)C.[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37]>>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[NH2:30][C:28]1[N:29]=[C:25]([NH:24][CH2:23][CH2:22][NH2:21])[S:26][C:27]=1[C:31]#[N:32]
Reactant: CC(C)(C)OC(=O)NCCNc1nc(N)c(C#N)s1
Agent: Cl
Agent: N#Cc1ccc(NCCN)nc1
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1sc(NCCN)nc1N

Procedure:
Analogously to the preparation of the cyanopyridine (Example 2A), 130 mg (0.46 mmol) of the Boc-protected amine (Example 15A) and 1.05 g (9.18 mmol) of trifluoroacetic acid gave, after removal of all volatile components, 130 mg (96% of theory) of the product.
Reaction SMILES: O(C(O[CH2:11][C:12]1[N:13]=[CH:14][N:15]([CH2:17][CH2:18][CH2:19][O:20][C:21]2[C:26]([CH3:27])=[CH:25][C:24]([C:28]3[N:29]=[N:30][N:31]([CH3:33])[N:32]=3)=[CH:23][C:22]=2[CH3:34])[N:16]=1)=S)C1C=CC=CC=1.CC(N=NC(C#N)(C)C)(C#N)C.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[CH3:11][C:12]1[N:13]=[CH:14][N:15]([CH2:17][CH2:18][CH2:19][O:20][C:21]2[C:22]([CH3:34])=[CH:23][C:24]([C:28]3[N:29]=[N:30][N:31]([CH3:33])[N:32]=3)=[CH:25][C:26]=2[CH3:27])[N:16]=1
Reactant: Cc1cc(-c2nnn(C)n2)cc(C)c1OCCCn1cnc(COC(=S)Oc2ccccc2)n1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: Cc1ccccc1
Product: Cc1ncn(CCCOc2c(C)cc(-c3nnn(C)n3)cc2C)n1
Temperature: 75 °C
Reaction time: 6.5 h
Yield: 54.9 %

Procedure:
To a solution of 5-phenoxythiocarbonyloxymethyl-2-[3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propyl]-1,2,4-triazole (130 mg, 0.79 mmol) in 20 ml of toluene was added AIBN (130 mg, 0.79 mmol) and tributyltin hydride (3.2 g, 11 mmol) and the mixture was stirred at 75° C. for 6.5 h. The solvent was concentrated in vacuo and the residue was purified by silica column chromatography (10 cm column, ethyl acetate/hexane, 1/1-5/1; methylene chloride/acetone, 4/1-0/1) to afford 142 mg (43%) of 5-methyl-2-[3-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-propyl]-1,2,4-triazole, m.p. 101°-103° C.
Reaction SMILES: [N+:1]([C:4]1[C:9](Cl)=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])([O-:3])=[O:2].[Cl:17][C:18]1[CH:19]=[C:20]([OH:25])[CH:21]=[C:22]([Cl:24])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>>[N+:1]([C:4]1[C:9]([O:25][C:20]2[CH:19]=[C:18]([Cl:17])[CH:23]=[C:22]([Cl:24])[CH:21]=2)=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])([O-:3])=[O:2]
Reactant: CCOC(=O)Cc1cccc(Cl)c1[N+](=O)[O-]
Reactant: Oc1cc(Cl)cc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCOC(=O)Cc1cccc(Oc2cc(Cl)cc(Cl)c2)c1[N+](=O)[O-]

Procedure:
A mixture of ethyl 2-(2-nitro-3-chlorophenyl)acetate (10 g.), 3,5-dichlorophenol (7.4 g.), anhydrous potassium carbonate (8.5 g.) and cupric oxide (1 g.) was treated in a similar manner to the above to give oil of the captioned compound (7.6 g.).