Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C@H:25]([C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=4)[C@@H:26]([NH2:28])[CH3:27])=[CH:21][CH:22]=3)[CH:17]=[N:16]2)=[CH:11][CH:10]=1.[NH2:37][C:38](=[O:42])[C:39](O)=[O:40].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[F:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C@H:25]([C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=4)[C@@H:26]([NH:28][C:39]([C:38]([NH2:37])=[O:42])=[O:40])[CH3:27])=[CH:21][CH:22]=3)[CH:17]=[N:16]2)=[CH:13][CH:14]=1
Reactant: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
Reactant: NC(=O)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC(C)NC(C)C
Solvent: ClCCl
Product: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)C(N)=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.4 %

Procedure:
N,N-Diisopropylamine (0.049 mL, 0.30 mmol) was added to a suspension of (1R,2S)-1-(1-(4-fluorophenyl)indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (53 mg, 0.14 mmol), 2-amino-2-oxoacetic acid (12 mg, 0.14 mmol) and HBTU (62 mg, 0.16 mmol.) in dichloromethane (2 mL). The mixture was stirred at r.t. overnight. The clear solution was concentrated and purified by HPLC to give the title compound (43 mg, 69%).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])=[CH:19][CH:18]=2)=[C:12]([CH:15]=1)[C:13]#[N:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=[O:33])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([C:8]1[CH:15]=[C:12]([C:13]([NH2:14])=[O:33])[C:11]2[NH:16][C:17]3[C:22]([C:10]=2[CH:9]=1)=[CH:21][C:20]([C:23]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[O:24])=[CH:19][CH:18]=3)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1cc(Cc2ccccc2)ccc1Nc1ccc(C(=O)N2CCOCC2)cc1
Reactant: CC(=O)O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Product: NC(=O)c1cc(Cc2ccccc2)cc2c1[nH]c1ccc(C(=O)N3CCOCC3)cc12
Temperature: 130 °C

Procedure:
A 5-ml microwave vial was loaded with 5-benzyl-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile (42 mg, 0.080 mmol), acetic acid (4 mL) and palladium acetate (45.1 mg, 0.201 mmol). The flask was sealed and heated to 130° C. for 13 hours. The reaction mixture was filtered through a 0.45 um Nylon filter and concentrated in vacuum. The crude was filtered through a layer of BIOTAGE® Si-propylthiol resin (0.8 g in a 6 ml cartridge, to remove Pd) and rinsed with methanol. The pale yellow eluent was concentrated and purified by prep HPLC to give 7.0 mg 3-benzyl-6-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide. MS (ESI) m/e−412, m/e+=414 consistent with [M−H]− and [M+H]+ resp. HPLC retention time 9.14 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (CD3OD) δ ppm 8.18 (m, 2H), 7.87 (s, 1H), 7.65 (b, 1H), 7.52 (b, 1H), 7.30 (m, 4H), 7.20 (b, 1H), 4.21 (s, 2H), 3.90-3.50 (b, 8H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([Cl:26])[CH:25]=1)[CH2:5][NH:6][C:7]([C:9]1([C:16]2[CH:21]=[CH:20][C:19](I)=[CH:18][CH:17]=2)[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1)=[O:8].[C:27]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)#[N:28].C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([Cl:26])[CH:25]=1)[CH2:5][NH:6][C:7]([C:9]1([C:16]2[CH:21]=[CH:20][C:19]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([C:27]#[N:28])[CH:34]=3)=[CH:18][CH:17]=2)[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1)=[O:8]
Reactant: N#Cc1cccc(B(O)O)c1
Reactant: CN1CCC(C(=O)NCc2cc(Cl)cc(Cl)c2)(c2ccc(I)cc2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: CN1CCC(C(=O)NCc2cc(Cl)cc(Cl)c2)(c2ccc(-c3cccc(C#N)c3)cc2)CC1
Temperature: 25 °C
Yield: 8.8 %

Procedure:
To a solution of 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid pyridine salt (0.44 g, 1.04 mmol, see Example 6) and 3,5-dichlorobenzylamine (0.22 g, 1.24 mmol, 1.2 eq) in anhydrous DMF (5 mL) was added DIC (0.326 mL, 2.08 mmol, 2 eq) followed by DMAP (0.006 g, 0.052 mmol, 5%). The mixture was stirred at room temperature for 16 h and then it was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The organic layer was separated, washed with H2O (3×40 mL) and saturated brine (50 mL), dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude material was purified by silica gel chromatography by eluting with 10% MeOH/EtOAc to give 60 mg (11%) of 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid 3,5-dichloro-benzylamide as a white solid. MS(ESI): 503.1/505.1. To a flask containing 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid 3,5-dichloro-benzylamide (60 mg, 0.12 mmol) was added Pd(PPh3)4 (3.2 mg, 0.012 mmol, 10 mol %), 3-cyanophenylboronic acid (26.4 mg, 0.18 mmol, 1.5 eq.) and Na2CO3 (0.21 g, 2 mmol). The mixture was suspended in toluene (2 mL), EtOH (1 mL) and H2O (1 mL) and heated at 90° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation. The crude product was purified by HPLC to give 4-(3′-cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid 3,5-dichloro-benzylamide as a white solid (0.05 g, 0.0105 mmol, 10%). 1H NMR (300 MHz, CDCl3): δ 7.88 (m, 2H), 7.71 (m, 3H), 7.52 (d, 2H), 7.31 (t, 1H), 7.00 (dd, 2H), 6.55 (t, 1H), 4.55 (br, 1H), 4.44 (d, 2H), 3.76 (m, 2H). 3.32 (m, 2H), 2.94 (s, 3H), 2.86 (m, 2H). 2.52 (t, 2H). MS (ESI): 478.1/480.1.
Reaction SMILES: I[C:2]1[C:10]2[N:9]=[N:8][N:7]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:23][CH2:22][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:20][CH2:19]4)[N:12]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][NH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[CH3:27][S:24]([N:21]1[CH2:22][CH2:23][CH:18]([NH:17][C:13]2[N:12]=[C:11]([N:7]3[C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([C:33]5[C:29]([CH3:28])=[N:30][NH:31][CH:32]=5)[C:10]=4[N:9]=[N:8]3)[CH:16]=[CH:15][N:14]=2)[CH2:19][CH2:20]1)(=[O:26])=[O:25]
Reactant: CS(=O)(=O)N1CCC(Nc2nccc(-n3nnc4c(I)cccc43)n2)CC1
Reactant: Cc1n[nH]cc1B1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: Cc1n[nH]cc1-c1cccc2c1nnn2-c1ccnc(NC2CCN(S(C)(=O)=O)CC2)n1
Temperature: 110 °C
Reaction time: 8 h
Yield: 149.7 %

Procedure:
A mixture of [4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-yl]-(1-methanesulfonyl-piperidin-4-yl)-amine (250 mg), 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg) and Na2CO3 (2 M aq, 0.7 mL, degassed), toluene (9 mL, degassed) and EtOH (0.7 mL) was added to a screw cap pressure flask. To this was added Pd(PPh3)4 (20 mg), the flask sealed, and the mixture stirred overnight at 110° C. The reaction mixture was then cooled to RT, and additional portions of 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg), Pd(PPh3)4 (20 mg), and EtOH (5 mL) added. The flask was again sealed and heated overnight at 110° C. The reaction mixture was then diluted in water, extracted in DCM, washed with water and brine, dried over Na2SO4, and the solvent stripped to yield a solid (0.34 g). The solid was chromatographed on silica, eluting with 0-60% Magic Base/DCM, then chromatographed again on silica using 0-60% Magic Base/DCM. The product was titurated with Et2O, filtered, and dried in vacuo overnight to provide (1-methanesulfonyl-piperidin-4-yl)-{4-[4-(3-methyl-1H-pyrazol-4-yl)-benzotriazol-1-yl]-pyrimidin-2-yl}-amine (Compound 10, 39 mg). Mp=231-232° C.; M+H=454.
Reaction SMILES: [CH3:1][N:2]1[C@@H:12]2[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]4[O:21][C@H:6]5[C:7]([CH2:9][CH2:10][C@:11]2([O:22][CH3:23])[C@:5]5([C:15]=34)[CH2:4][CH2:3]1)=[O:8].[CH3:24][I:25]>C(#N)C>[I-:25].[O:21]1[C@@H:6]2[C@@:5]34[CH2:4][CH2:3][N+:2]([CH3:24])([CH3:1])[C@@H:12]([C@:11]3([O:22][CH3:23])[CH2:10][CH2:9][C:7]2=[O:8])[CH2:13][C:14]2=[C:15]4[C:16]1=[C:17]([OH:20])[CH:18]=[CH:19]2
Reactant: CO[C@@]12CCC(=O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
Reactant: CI
Solvent: CC#N
Product: CO[C@@]12CCC(=O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CC[N+](C)(C)[C@@H]2C5
Product: [I-]
Reaction time: 24 h

Procedure:
A solution of 14-O-methyloxymorphone (Schmidhammer et al., J. Med. Chem. 1984, 27, pp. 1575-1579) (200 mg, 0.63 mmol) and methyl iodide (0.32 ml, 5.07 mmol) in acetonitrile (10 ml) was stirred for 21 hours under N2 at 50° C. (bath temperature). Then methyl iodide (0.2 ml, 3.17 mmol) was again added, stirred further for 24 h under the same conditions and evaporated down. The evaporation residue (324 mg of brown foamy resin) was crystallised out of MeOH (0.5 ml) and purified by recrystallisation out of MeOH. Yield: 244 mg (84%) of compound 44. Fp. 225-240° C.; IR (KBr): 1725 (C═O) cm−1; 1H-NMR (DMSO-d6): δ 9.55 (s, C3—OH), 6.69 (s, 2 arom. H, C1—H, C2—H), 4.94 (s, C5—H), 3.55 (s, +NCH3, axial), 3.38 (s, OCH3), 3.22 (s, +NCH3, equatorial); MS (CI): m/z 330 (M+).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:22](C)=O.[Na+].CCCCCC.C(OCC)(=O)C>O>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([NH:15][CH3:22])=[CH:16][CH:17]=1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: COCCOCOCCOc1ccc(N)cc1
Agent: C=O
Agent: [Na+]
Solvent: O
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CNc1ccc(OCCOCOCCOC)cc1
Reaction time: 0.17 h
Yield: 18.9 %

Procedure:
To a 25 mL, 3-neck RBF equipped with a magnetic stirrer and calcium chloride guard tube, 4-(2-((2-methoxyethoxy)methoxy)ethoxy)aniline (1.0 g in 10 mL DMF) and formaldehyde (0.062 g) were added portion wise to the reaction mixture at 0° C. and stirred for an additional 10 minutes. NaBH(OAc)3 (0.88 g) was added and the mixture was stirred for 5 minutes. The reaction was monitored on TLC using hexane:ethyl acetate (5:5) as mobile phase. After completion of the reaction, the reaction mixture was poured in water and extracted with ethyl acetate. Organic layer was washed with brine, dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. Crude material was purified by using column chromatography. Desired product was eluted with 7% ethyl acetate in hexane to give 0.200 g of 4-(2-((2-methoxyethoxy)methoxy)ethoxy)-N-methylaniline. M+1=256.0.
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:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[CH:30][C:29]=2[O:40][CH3:41])[C:24]([Cl:42])=[CH:23][N:22]=1>>[Cl:42][C:24]1[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[CH:30][C:29]=2[O:40][CH3:41])=[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: COc1cc(N2CCOCC2)ccc1Nc1nc(Cl)ncc1Cl
Reactant: COc1cc2c(cc1N)CCN(CC(C)(F)F)CC2
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccc(N4CCOCC4)cc3OC)n1)CCN(CC(C)(F)F)CC2

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 (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine in an analogous manner to Example 61e. Product isolated as an off-white solid (0.047 g, 57%). MP: 215-220° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.23 (d, 1H, J=8.8 Hz), 8.10 (s, 1H), 8.01 (s, 1H), 7.51 (s, 1H), 7.44 (s, 1H), 6.62 (s, 1H), 6.54 (d, 1H, J+2.3 Hz), 6.50 (dd, 1H, J=8.8 Hz and 2.0 Hz), 3.91 (s, 3H), 3.90-3.87 (m, 4H), 3.86 (s, 3H), 3.18-3.12 (m, 4H), 2.90-2.76 (m, 10H), 1.68 (t, 3H, J=18.7 Hz). MS: 589 (MH)+.
Reaction SMILES: [Li+].[Cl-].[C:3]([O:7][C:8](=[O:23])[NH:9][CH2:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[C:14]([NH2:21])=[C:13](I)[CH:12]=1)([CH3:6])([CH3:5])[CH3:4].[CH2:24](C([Sn])=C(CCCC)CCCC)[CH2:25]CC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[C:3]([O:7][C:8](=[O:23])[NH:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:24]=[CH2:25])[C:14]([NH2:21])=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)([CH3:6])([CH3:5])[CH3:4]
Reactant: CC(C)(C)OC(=O)NCc1cc(I)c(N)c(C(F)(F)F)c1
Reactant: CCCCC([Sn])=C(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: C=Cc1cc(CNC(=O)OC(C)(C)C)cc(C(F)(F)F)c1N

Procedure:
Pd(PPh3)4 (0.06 eq, 0.014 mmol, 16.64 mg) and LiCl (2.8 eq, 0.67 mmol, 28.49 mg) were added into DMF. (4-Amino-3-iodo-5-trifluoromethylbenzyl)carbamic acid tert-butyl ester (100 mg, 0.24 mmol) and tributylvinyltin (1.5 eq, 0.36 mmol, 105.37 μl) were added into the reaction mixture. The reaction mixture was stirred for 12 ha in reflux. The reaction mixture was purified according to step 4 of Example 8 to give a title product, yellow syrup (51.5 mg, 67.87%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([C:10]#[N:11])[CH:8]=[CH:9][C:2]1=2.C([Li])CCC.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C>C1COCC1>[C:10]([C:7]1[CH:8]=[CH:9][C:2]2[S:1][C:5]([B:17]([OH:22])[OH:18])=[CH:4][C:3]=2[CH:6]=1)#[N:11]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: N#Cc1ccc2sccc2c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: N#Cc1ccc2sc(B(O)O)cc2c1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a cold (−78° C.) solution of benzo[b]thiophene-5-carbonitrile (276 mg, 1.734 mmol) in anhydrous THF (5 mL) was added n-butyllithium (0.763 mL, 1.907 mmol) dropwise. The reaction mixture was stirred at −78° C. for 60 minutes. Next, a solution of triisopropyl borate (0.478 mL, 2.080 mmol) was added. The reaction mixture was stirred for 30 minutes stirring at −78° C. and then was allowed to warm to room temperature over a 2 hour period. Solvent was removed to give the title compound, which was used without purification or work up.
Reaction SMILES: [Na+].[OH:2]C1C=CC(S([O-])(=O)=O)=CC=1[N+]([O-])=O.[CH:16]1([N:22]=[C:23]=[N:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C)C=O>[CH:25]1([NH:24][C:23](=[O:2])[NH:22][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)[O-])ccc1O
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(NC1CCCCC1)NC1CCCCC1

Procedure:
One molar equivalent (2.24 g) of 4-hydroxy-3-nitro-benzene sulfonic acid sodium salt (HNSA) is mixed together with one molar equivalent (2.06 g) of dicyclohexylcarbodiimide and one molar equivalent (2.10 g) of N-maleimido-6-aminocarpoic acid in 25 ml of dimethylformamide (DMF) at room temperature overnight. A white precipitate of dicyclohexyl urea is formed. The precipitate is filtered and 300 ml diethyl ether is added to the mother liquor. After about 10 minutes to 4 hours a gummy solid precipitated from the mother liquor is formed. This solid will contain 58% of active HNSA ester and 42% of free HNSA.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6]([N+:10]([O-])=O)=[CH:5][CH:4]=1.[H][H]>C(O)C.[Pd]>[CH3:1][O:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6]([NH2:10])=[CH:5][CH:4]=1
Reactant: COc1ccc([N+](=O)[O-])c(N)n1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COc1ccc(N)c(N)n1

Procedure:
6-(Methyloxy)-3-nitro-2-pyridinamine (26 g, 129 mmol) was suspended in ethanol (500 ml) at room temperature under argon and then treated with palladium on carbon (15 g, 14.10 mmol) (10% paste). The reaction was stirred under 1 atm of hydrogen overnight. The reaction was filtered through a Celite pad and the pad washed with ethanol (500 ml). Ethanol was evaporated to afford the product as a purple oil (20.68 g, slightly impure).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH3:6][S:7][CH:8]1[N:13](C)[C:12](O)=[C:11]([Br:16])[CH:10]=[N:9]1.[CH3:17]CN(CC)CC>C(Cl)Cl>[Br:16][C:11]1[C:10]([CH2:1][S:2]([CH3:17])(=[O:4])=[O:3])=[N:9][C:8]([S:7][CH3:6])=[N:13][CH:12]=1
Reactant: CSC1N=CC(Br)=C(O)N1C
Reactant: CS(=O)(=O)Cl
Reactant: CCN(CC)CC
Solvent: ClCCl
Product: CSc1ncc(Br)c(CS(C)(=O)=O)n1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
MsCl (5.85 g, 51.0 mmol) was added to a stirred, cooled 0° C. mixture of 2-methylthio-5-bromo-3-methylhydroxy pyrimidine (10 g, 42.5 mmol) in CH2Cl2 (200 mL), followed by addition of Et3N (6.46 g, 63.8 mmol). The mixture was stirred at 0° C. for 30 min. TLC showed no starting material left. The mixture was quenched with water (30 mL) and the mixture was washed with more water (50 mL). The organic fraction were washed with brine (saturated, 50 mL), dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 65i, eluting with EtOAc/hexane (3/7) to give the title compound as a colorless solid. 1H NMR (CDCl3, 500 MHz) δ 8.61 (s, 1H), 5.38 (s, 2H), 3.21 (s, 3H), 2.60 (s, 3H).
Reaction SMILES: [OH-].[Na+].[CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1/[C:13](/[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:14]\[C:15]([O:17]CC)=[O:16].O.Cl>C(O)C.O1CCCC1>[CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1/[C:13](/[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:14]\[C:15]([OH:17])=[O:16]
Reactant: CCOC(=O)/C=C(/c1ccccc1)c1ccc2ccccc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: O=C(O)/C=C(/c1ccccc1)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 91.7 %

Procedure:
24 ml of a 10% w/v aqueous solution of sodium hydroxide were added to a solution of 2.411 g of ethyl (Z)-3-(2-naphthyl)-3-phenylacrylate (prepared as described in Preparation 112) in 48 ml of ethanol and 24 ml of tetrahydrofuran. The mixture was stirred for 15 hours at room temperature and then poured into water. The pH of the resulting mixture was adjusted to a value of 2 by the addition of concentrated hydrochloric acid, and the mixture was then extracted twice with methylene chloride. The combined extracts were washed with water and dried over anhydrous sodium sulfate; the solvent was then removed by evaporation under reduced pressure. The residue was recrystallized from a mixture of methylene chloride and hexane, to give 2.005 g of the title compound, melting at 170°-172° C.
Reaction SMILES: [CH2:1]([OH:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:11](I)[CH3:12]>>[CH2:1]([O:10][CH2:11][CH3:12])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CCI
Reactant: OCC=Cc1ccccc1
Product: CCOCC=Cc1ccccc1

Procedure:
Reaction of cinnamyl alcohol with ethyl iodide was carried out in the same manner as described in Example I. The analytical data supported the assigned structure and GC analysis indicated a purity of 99+%: λmaxCCl4 6.66, 6.87, 7.25, 8.75-9.1, 10.35 and 14.45 μ.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:10][CH:11]=[CH2:12])[CH:6]=[CH:7][C:8]=1[OH:9].[CH2:13]([O:15][SiH:16]([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19])[CH3:14]>[Pt].[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl.C(O)(C)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:10][CH2:11][CH2:12][Si:16]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])[O:15][CH2:13][CH3:14])[CH:6]=[CH:7][C:8]=1[OH:9]
Reactant: C=CCc1ccc(O)c(OC)c1
Reactant: CCO[SiH](OCC)OCC
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [Pt]
Agent: [H+]
Solvent: CC(C)O
Product: CCO[Si](CCCc1ccc(O)c(OC)c1)(OCC)OCC
Temperature: 55 °C
Yield: 88 %

Procedure:
Into a four-neck flask provided with a stirrer, a reflux condenser, a dropping funnel and a thermometer were added 164 g (1.0 mole) of 3-(3-methoxy-4-hydroxyphenyl)propene and 100 ppm in terms of platinum metal of a 2 mass % isopropanol solution of chloroplatinic acid. Then 164 g (1.0 mole) of triethoxysilane was dripped over the course of five hours from a dropping funnel and was reacted while the mixture was heated and stirred at a temperature in the range from 50 to 60° C. After the reaction was completed, vacuum distillation was performed and 289 g (0.88 mole) of the desired product (3-(3-methoxy-4-hydroxyphenyl)propyl triethoxysilane) were obtained. The yield was 88%.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH2:14])[C:8](=[CH:12][CH:13]=1)[C:9]([NH2:11])=[O:10])([O:3][CH3:4])=[O:2].Cl[C:16]1[S:17][CH:18]=[CH:19]N=1>>[S:17]1[C:16]2=[N:14][C:7]3[C:8]([C:9](=[O:10])[N:11]2[CH:19]=[CH:18]1)=[CH:12][CH:13]=[C:5]([C:1]([O:3][CH3:4])=[O:2])[CH:6]=3
Reactant: Clc1nccs1
Reactant: COC(=O)c1ccc(C(N)=O)c(N)c1
Product: COC(=O)c1ccc2c(=O)n3ccsc3nc2c1
Yield: 78.1 %

Procedure:
19.4 g of 4-carbomethoxyanthranilamide and 12 g of 2-chlorothiazole were stirred for 4 hours at 150° C. After working up in the conventional manner there was obtained 20.3 g (78%) of the above compound; m.p. 228°-230° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[O:6]C(=O)[CH:4]=1.[CH3:14][O-:15].[Mg+2].[CH3:17][O-:18]>>[F:10][C:9]([F:11])([F:12])[C:7](=[O:6])[CH2:8][C:3]([O:2][CH3:1])=[CH:4][C:14]([O:18][CH3:17])=[O:15]
Reactant: COc1cc(C(F)(F)F)oc(=O)c1
Reactant: C[O-]
Agent: [Mg+2]
Product: COC(=O)C=C(CC(=O)C(F)(F)F)OC
Yield: 82.5 %

Procedure:
A solution of 4-methoxy-6-trifluoromethylpyran-2-one (2.7 g, 14 mmol) in a methanolic magnesium methanolate solution (8.5% Mg(OMe)2, 8.36 g, 8 mmol) was heated under reflux for 16 hours. The solution was concentrated and taken up in water and ethyl acetate, and the organic phase was brought to pH 5 by adding dilute hydrochloric acid. The organic phase was separated off, dried and concentrated. 1.5 g of crude product were obtained as a yellow oil. Kugelrohr distillation at 0.04 mbar and about 160° C. afforded methyl 6,6,6-trifluoro-3-methoxy-5-oxo-2-hexenoate (1.50 g, 6.6 mmol, 48%) as a pale yellow oil.