Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH2:3]([NH:10][C:11]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[I-].CS[C:22]1[S:26][CH:25]=[CH:24][S+:23]=1>COCCOC>[S:23]1[CH:24]=[CH:25][S:26][C:22]1=[C:13]([C:11](=[O:12])[NH:10][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: CCOC(=O)CC(=O)NCc1ccccc1
Reactant: CSc1scc[s+]1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOC(=O)C(C(=O)NCc1ccccc1)=C1SC=CS1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 40.9 %

Procedure:
Sodium hydride (a 60% of dispersion in oil) (189 mg) is suspended in 1,2-dimethoxyethane (20 ml), and the mixture is cooled with ice-water. A solution of ethyl (N-benzylcarbamoyl)acetate (1.002 g) in 1,2-dimethoxyethane (23 ml) is added dropwise to the mixture. The mixture is stirred for 30 minutes. Then, 2-methylthio-1,3-dithiolium iodide (1.309 g) is added to the mixture, and the mixture is stirred at room temperature for 2 hours and then at 40° C. to 50° C. for one hour. After cooling, the mixture is poured into ice-water, and the aqueous solution is extracted with ethyl acetate. The extract is washed with water, dried and then evaporated to remove the solvent. The residue thus obtained is treated in the same manner as described in Example 22-(2), whereby ethyl 2-(1,3-dithiol-2-ylidene)-2-(N-benzylcarbamoyl)acetate (595 mg) is obtained.
Reaction SMILES: [F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH:8]2[CH2:14][NH:13][CH:12]([CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:18].[I:19][C:20]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:21]=1[C:22](O)=[O:23].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH:8]2[CH2:14][N:13]([C:22](=[O:23])[C:21]3[CH:25]=[C:26]([CH3:29])[CH:27]=[CH:28][C:20]=3[I:19])[CH:12]([CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:18]
Reactant: Cc1ccc(I)c(C(=O)O)c1
Reactant: Cc1cc(OCC2CCCC(C)NC2)ccc1F
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(I)c(C(=O)N2CC(COc3ccc(F)c(C)c3)CCCC2C)c1
Temperature: 23 °C
Reaction time: 16 h

Procedure:
A solution of 6-[(4-fluoro-3-methylphenoxy)methyl]-2-methylazepane (2-7, 120 mg, 0.48 mmol, 1.0 equiv) in DMF (5 mL) was treated with 2-iodo-5-methylbenzoic acid (140 mg, 0.52 mmol, 1.1 equiv), EDC (110 mg, 0.57 mmol, 1.2 equiv), HOBT (88 mg, 0.57 mmol, 1.2 equiv) and triethylamine (0.20 mL, 140 mg, 1.4 mmol, 3.0 equiv) and the resulting mixture was stirred at 23° C. for 16 hours. The mixture was filtered and purified by reverse phase liquid chromatography (Sunfire C18 OBD 5 um, 20×150 mm column; 0-100% CH3CN/H2O gradient w/0.10% TFA present) to yield 6-[(4-fluoro-3-methylphenoxy)methyl]-1-(2-iodo-5-methylbenzoyl)-2-methylazepane (3-1). δ 7.87 (m, 1H), 7.10 (m, 6H), 6.43 (m, 1H), 4.79-1.04 (m, 19H). LRMS m/z (M+H) 496.2 found, 496.1 required.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:65]=[CH:64][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][C:57]=2[Cl:63])=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:65]=[CH:64][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][C:57]=2[Cl:63])[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
Reactant: CC(C)(C)c1ccc(CNCCc2ccc(Cl)cc2Cl)cc1
Reactant: O=C(O)c1cccc2cc[nH]c12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)c1ccc(CN(CCc2ccc(Cl)cc2Cl)C(=O)c2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 88.9 %

Procedure:
To a solution of 81 mg of 1H-indole-7-carboxylic acid (0.5 mmol) and 161 mg of TBTU (0.5 mmol) in 10 ml DMF, were added 0.43 ml (2.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 168 mg (0.5 mmol) of (4-tert-butyl-benzyl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine were added. After stirring for 3 h at rt, the reaction mixture was diluted with 50 ml water and extracted twice with EtOAc. The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (40 g silica gel; heptane/EtOAc 2:1) to give 213 mg (87%) of a light yellow oil. MS(ISP) 479.4 (M+H)+.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH:3]([C:6]([OH:8])=O)[CH2:2]1.CCN=C=NCCCN(C)C.Cl.O.ON1C2C=CC=CC=2N=N1.[O:32]1[CH2:37][CH2:36][CH:35]([C:38]([C:40]2[S:44][C:43]([NH2:45])=[N:42][C:41]=2[C:46]2[O:47][CH:48]=[CH:49][CH:50]=2)=[O:39])[CH2:34][CH2:33]1.C(=O)([O-])O.[Na+]>>[O:47]1[CH:48]=[CH:49][CH:50]=[C:46]1[C:41]1[N:42]=[C:43]([NH:45][C:6]([CH:3]2[CH2:4][CH2:5][O:1][CH2:2]2)=[O:8])[S:44][C:40]=1[C:38]([CH:35]1[CH2:36][CH2:37][O:32][CH2:33][CH2:34]1)=[O:39]
Reactant: Nc1nc(-c2ccco2)c(C(=O)C2CCOCC2)s1
Reactant: O=C(O)C1CCOC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: O
Product: O=C(Nc1nc(-c2ccco2)c(C(=O)C2CCOCC2)s1)C1CCOC1
Temperature: 60 °C
Reaction time: 3.5 h
Yield: 83.8 %

Procedure:
Tetrahydrofuran-3-carboxylic acid (1.72 mL, 1.8 mmol), EDC hydrochloride (344 mg, 1.80 mmol) and 1-hydroxybenzotriazole monohydrate (276 mg, 1.80 mmol) were added to Compound 454 (125 mg, 0.450 mmol), followed by stirring at 60° C. for 3.5 hours. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was reslurried with diethyl ether to afford the entitled Compound 524 (142 mg, 84%).
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([S:12]([CH3:15])(=[O:14])=[O:13])=[C:8]([C:10]#[N:11])[CH:9]=1)=[O:4].[Li+].[OH-].Cl.C(C1C=C(C(O)=O)SC=1S(C)(=O)=[O:27])#N>C1COCC1.O>[C:10]([C:8]1[CH:9]=[C:5]([C:3]([OH:2])=[O:4])[S:6][C:7]=1[S:12]([CH3:15])(=[O:14])=[O:13])(=[O:27])[NH2:11]
Reactant: CS(=O)(=O)c1sc(C(=O)O)cc1C#N
Reactant: COC(=O)c1cc(C#N)c(S(C)(=O)=O)s1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CS(=O)(=O)c1sc(C(=O)O)cc1C(N)=O

Procedure:
To 4-cyano-5-methanesulfonyl-thiophene-2-carboxylic acid methyl ester (0.5 g) in THF/H2O (3:1; 16 ml) was added LiOH (0.102 g). Hydrochloric acid (2M) was added and the resulting mixture was extracted with ethyl acetate. The extracts were combined and the solvent evaporated to leave a mixture of 4-cyano-5-methanesulfonyl-thiophene-2-carboxylic acid and the title compound. This mixture was used without further purification. 1H NMR (299.944 MHz, DMSO-D6) δ 3.62 (3H, s), 7.99 (1H, s).
Reaction SMILES: C[O:2][C:3]1[C:4]([N+:21]([O-:23])=[O:22])=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:9][CH2:8][C:7]=2[N:20]=1.Br.CC(O)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O>[CH3:13][CH:12]1[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:9][CH2:8][C:7]2[N:20]=[C:3]([OH:2])[C:4]([N+:21]([O-:23])=[O:22])=[CH:5][C:6]1=2
Reactant: COc1nc2c(cc1[N+](=O)[O-])C(C)CN(C(=O)C(F)(F)F)CC2
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC1CN(C(=O)C(F)(F)F)CCc2nc(O)c([N+](=O)[O-])cc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 87.7 %

Procedure:
A mixture of 2-methoxy-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (2.00 g, 6.00 mmol), HBr/AcOH (33 wt %, 20 ml) and H20 (5 ml) was stirred for 10 min at room temperature. The reaction was parted between sat. aq. NaHCO3 and EtOAc. The organic phased was dried and concentrated in vacuo to give 1.68 g (88%) of pure 5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol. 1H-NMR (CDCl3) δ 8.42 (s, 1H), 4.20-3.20 (m, 8H), 1.45 (d, 1.2H), 1.39 (d, 1.8H) ppm. A mixture of 5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (1.63 g, 5.10 mmol), Bu4NBr (4.94 g, 15.3 mmol), P2O5 (3.62 g, 12.8 mmol) and toluene (100 ml) was heated to 110° C. for 5 h. The reaction was cooled to room temperature and the liquid part was decanted and concentrated in vacuo to give 1.25 g (64%) of pure 2-bromo-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 8.05 (s, 1H), 3.80 (m, 3H), 3.60-3.25 (m, 4H), 1.41 (d, 1.2H), 1.35 (d, 1.8H) ppm. Concurent reduction of the nitro group and halogene on was carried out with 5% Pd/C in MeOH under H2 (1 atm) to give 1.20 g (97%) of pure 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR of rotamers (MeOH-d4) δ 7.77 (2× d, 1H), 7.62 (d, 0.4H), 7.58 (d, 0.6H), 4.10-3.35 (m, 7H), 1.42 (d, 1.3H), 1.35 (d, 1.7H) ppm. A mixture of 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (130 mg, 476 μmol), K2CO3 (100 mg), MeOH (6 ml) and H2O (1 ml) was stirred for 16 h at room temprature. The reaction mixture was parted between aq. NaHCO3 and DCM, the organic layer was dried and then concentrated in vacuo. The resulting residue was purified by column chromatography to yield 20.0 mg (24%) of 5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NNMR (MeOH-d4) δ 7.68 (s, 1H), 7.24 (s, 1H), 3.45-2.95 (m, 7H), 1.37 (d, 3H) ppm.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:10][O:11][C:12](=[O:35])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2I)[C:21](=[O:27])[C:22]#[C:23][CH:24]([CH3:26])[CH3:25])[CH:14]=1>>[CH3:10][O:11][C:12](=[O:35])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:20]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)/[C:22](=[C:23](\[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)/[CH:24]([CH3:26])[CH3:25])/[C:21]2=[O:27])[CH:14]=1
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)c1cccc(CN(C(=O)C#CC(C)C)c2ccccc2I)c1
Product: COC(=O)c1cccc(CN2C(=O)/C(=C(/c3ccccc3)C(C)C)c3ccccc32)c1

Procedure:
The title compound was prepared in analogy to Example 84 starting from phenylboronic acid (commercially available) and 3-{[(2-iodo phenyl)-(4-methyl-pent-2-ynoyl)-amino]-methyl}-benzoic acid methyl ester. 1H NMR (CDCl3, 300 MHz) δppm 8.04 (s, 1H), 7.94 (d, 1H), 7.48-7.53 (m, 3H), 7.39 (t, 1H), 7.15 (dd, 2H), 6.99 (t, 1H), 6.59-6.61 (d, 1H), 6.55 (t, 1H), 5.59 (d, 2H), 5.00-5.05 (m, 3H), 3.97 (s, 3H), 1.11 (s, 3H), 1.09 (s, 3H).
Reaction SMILES: [CH:1](=[N:6][OH:7])[C:2]([CH3:5])([CH3:4])[CH3:3].ClN1C(=O)CCC1=O.[Cl-].[CH:17]([P:19]([CH3:23])(=[O:22])[O:20][CH3:21])=[CH2:18].C(N(CC)CC)C>ClCCl.N1C=CC=CC=1>[C:2]([C:1]1[CH2:18][CH:17]([P:19]([CH3:23])(=[O:22])[O:20][CH3:21])[O:7][N:6]=1)([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)C=NO
Reactant: C=CP(C)(=O)OC
Agent: O=C1CCC(=O)N1Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: COP(C)(=O)C1CC(C(C)(C)C)=NO1
Yield: 50 %

Procedure:
40.4 g (0.4 mol) of pivalaldoxime are converted in analogy to Example 1(a) with 58.7 g (0.44 mol) of N-chlorosuccinimide and 2 ml of pyridine in dichloromethane into the hydroxamoyl chloride which is subsequently reacted with 52.8 g (0.44 mol) of methyl vinyl(P-methyl)phosphinate and 61.2 ml (0.44 mol) of triethylamine, and worked up, as described in Example 1(b), the oily product being obtained with a yield of about 50%.
Reaction SMILES: [CH3:1]CCCCCCCCCCCCCCCOC(CCCCCC(C)C)=O.CCCCCCCC/C=C\CCCCCC[CH2:44][CH2:45][O:46][C:47]([CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55]/[CH:56]=[CH:57]\[CH2:58][CH2:59][CH2:60][CH2:61]CCCC)=[O:48]>>[C:47]([O:46][CH:45]([CH3:44])[CH3:1])(=[O:48])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61]
Reactant: CCCCCCCCCCCCCCCCOC(=O)CCCCCC(C)C
Reactant: CCCCCCCC/C=C\CCCCCCCCOC(=O)CCCCCCC/C=C\CCCCCCCC
Product: CCCCCCCCCCCCCC(=O)OC(C)C

Procedure:
cetearyl isononanoate--"Cetiol SN": 8.00 wt. %
Reaction SMILES: [C:1]1([CH2:17][C:18]([O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][OH:26])=[O:19])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[F:27][C:28]([F:125])([F:124])[C:29]([F:123])([F:122])[C:30]([F:121])([F:120])[C:31]([F:119])([F:118])[C:32]([F:117])([F:116])[C:33]([F:115])([F:114])[C:34]([F:113])([F:112])[C:35]([F:111])([F:110])[CH2:36][CH2:37][CH2:38][CH2:39][O:40][C:41]1[CH:42]=[C:43]([CH:47]=[C:48]([O:80][CH2:81][CH2:82][CH2:83][CH2:84][C:85]([F:109])([F:108])[C:86]([F:107])([F:106])[C:87]([F:105])([F:104])[C:88]([F:103])([F:102])[C:89]([F:101])([F:100])[C:90]([F:99])([F:98])[C:91]([F:97])([F:96])[C:92]([F:95])([F:94])[F:93])[C:49]=1[O:50][CH2:51][CH2:52][CH2:53][CH2:54][C:55]([F:79])([F:78])[C:56]([F:77])([F:76])[C:57]([F:75])([F:74])[C:58]([F:73])([F:72])[C:59]([F:71])([F:70])[C:60]([F:69])([F:68])[C:61]([F:67])([F:66])[C:62]([F:65])([F:64])[F:63])[C:44](O)=[O:45]>>[C:1]1([CH2:17][C:18]([O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][O:26][C:44](=[O:45])[C:43]2[CH:42]=[C:41]([O:40][CH2:39][CH2:38][CH2:37][CH2:36][C:35]([F:111])([F:110])[C:34]([F:113])([F:112])[C:33]([F:115])([F:114])[C:32]([F:117])([F:116])[C:31]([F:119])([F:118])[C:30]([F:121])([F:120])[C:29]([F:123])([F:122])[C:28]([F:125])([F:124])[F:27])[C:49]([O:50][CH2:51][CH2:52][CH2:53][CH2:54][C:55]([F:78])([F:79])[C:56]([F:76])([F:77])[C:57]([F:74])([F:75])[C:58]([F:72])([F:73])[C:59]([F:70])([F:71])[C:60]([F:68])([F:69])[C:61]([F:67])([F:66])[C:62]([F:63])([F:64])[F:65])=[C:48]([O:80][CH2:81][CH2:82][CH2:83][CH2:84][C:85]([F:108])([F:109])[C:86]([F:106])([F:107])[C:87]([F:104])([F:105])[C:88]([F:102])([F:103])[C:89]([F:101])([F:100])[C:90]([F:99])([F:98])[C:91]([F:96])([F:97])[C:92]([F:93])([F:94])[F:95])[CH:47]=2)=[O:19])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1
Reactant: O=C(O)c1cc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c1
Reactant: O=C(Cc1ccc2ccc3cccc4ccc1c2c34)OCCOCCO
Product: O=C(Cc1ccc2ccc3cccc4ccc1c2c34)OCCOCCOC(=O)c1cc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c1

Procedure:
As depicted in the Scheme below, 2-(2-Hydroxyethoxy)-ethyl (1-pyrenyl)-acetate is reacted with 3,4,5-tris-(12,12,12,11,11,10,10,9,9,8,8,7,7,6,6,5,5-heptadecafluoro-n-dodecan-1-yloxy)-benzoic acid to produce compound D3.
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([C:15]2[C@H:24]3[C@H:19]([CH2:20][CH2:21][CH2:22][CH2:23]3)[C:18](=[O:25])[N:17]([CH2:26][C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=3)[N:16]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14].[CH3:36]O>>[CH3:5][O:6][C:7]1[CH:8]=[C:9]([C:15]2[C@H:24]3[C@H:19]([CH2:20][CH2:21][CH2:22][CH2:23]3)[C:18](=[O:25])[N:17]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([C:31]([O:33][CH3:36])=[O:32])=[CH:34][CH:35]=3)[N:16]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14]
Reactant: CO
Reactant: COc1ccc(C2=NN(Cc3ccc(C(=O)O)cc3)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(CN2N=C(c3ccc(OC)c(OC)c3)[C@@H]3CCCC[C@@H]3C2=O)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
3 ml of thionyl chloride was added slowly to a solution of 1 g of compound 83 in methanol at -20° C. After complete addition, the mixture was stirred for 6 hours at room temperature and subsequently evaporated. The compound was crystallized from diethyl ether at -20° C. M.p. 90°-92° C.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].[C:25]([NH:32][C@H:33]([CH:38]=[O:39])[CH2:34][CH:35]([CH3:37])[CH3:36])([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].Cl>O1CCCC1>[NH:32]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[C@H:33]([C@H:38]([CH2:20][C:19]([O:22][CH2:23][CH3:24])=[O:21])[OH:39])[CH2:34][CH:35]([CH3:37])[CH3:36]
Reactant: CC(C)C[C@@H](C=O)NC(=O)OC(C)(C)C
Reactant: CCOC(C)=O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Product: CCOC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)OC(C)(C)C
Temperature: 10 °C
Reaction time: 0.25 h
Yield: 38.8 %

Procedure:
To diisopropylamine (7.7 gm, 0.077 mole) in dry tetrahydrofuran (26 mL) cooled to -20° C. under an argon atmosphere was added dropwise n-butyllithium in hexane (1.46 m, 52.4 mL, 0.077 mole). The solution was stirred 15 minutes, the temperature lowered to -78° C. and dry ethyl acetate (6.7 g. 0.077 mole) added dropwise while maintaining the temperature below -75° C. The solution was stirred 10 minutes and a precooled (-78° C.) tetrahydrofuran solution of Boc-L-leucinal (11 gm., 0.051 mole) was added. After 30 minutes, 2M HCl (40 mL) was added and the mixture was slowly warmed to 10° C. and extracted with ether (3×200 mL). The combined ethereal extract was washed with saturated sodium chloride (NaCl) and dried with magnesium sulfate (MgSO4) and filtered. Evaporation of the filtrate in vacuo gave 14 gm of crude product which was purified by flash column chromatography (20% ethylacetate in hexane). Obtained 6 gm of Boc-Sta-OEt.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]=O)=[CH:4][CH:3]=1.[Cl:11][C:12]1[N:20]=[C:19]2[C:15]([N:16]=[CH:17][N:18]2[CH2:21][CH:22]([CH3:24])[CH3:23])=C(Cl)[N:13]=1>>[Cl:11][C:12]1[N:20]=[C:19]2[C:15]([N:16]=[CH:17][N:18]2[CH2:21][CH:22]([CH3:24])[CH3:23])=[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:13]=1
Reactant: CC(C)Cn1cnc2c(Cl)nc(Cl)nc21
Reactant: O=CNc1ccc(Cl)cc1
Product: CC(C)Cn1cnc2c(Nc3ccc(Cl)cc3)nc(Cl)nc21

Procedure:
Was prepared according to Example 3 from N-(4-chloro-phenyl)-formamide and 2,6-dichloro-9-isobutyl-9H-purine.
Reaction SMILES: [CH3:1][C:2]([OH:16])([C:4]([C:6]1[CH:11]=[CH:10][C:9](OCCO)=[CH:8][CH:7]=1)=[O:5])[CH3:3].CC(N1CCOCC1)(C(C1C=CC(SC)=CC=1)=O)C.CCC(N(C)C)(C(C1C=CC(N2CCOCC2)=CC=1)=O)CC1C=CC=CC=1.C1C=CC(C(C(OCCOCCOC(C(C2C=CC=CC=2)=O)=O)=O)=O)=CC=1>C1C=C[CH]C=1.C1C=C[CH]C=1.C1C=CN([C]2C(F)=C=C(F)C=C2)C=1.C1C=CN([C]2C(F)=C=C(F)C=C2)C=1.[Ti]>[OH:16][C:2]([CH3:3])([CH3:1])[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5]
Reactant: CC(C)(O)C(=O)c1ccc(OCCO)cc1
Agent: [Ti]
Agent: CCC(Cc1ccccc1)(C(=O)c1ccc(N2CCOCC2)cc1)N(C)C
Agent: CSc1ccc(C(=O)C(C)(C)N2CCOCC2)cc1
Product: CC(C)(O)C(=O)c1ccccc1

Procedure:
Other examples are IRGACURE2959, IRGACURE127, IRGACURE907, IRGACURE369, IRGACURE379, DAROCUR TPO, IRGACURE819, IRGACURE784, IRGACURE OXE01, IRGACURE OXE02, and IRGACURE754 (all are manufactured by Ciba Specialty Chemicals).
Reaction SMILES: [O:1]=[C:2]1[C:6]([C:7]2[CH:8]=[N:9][CH:10]=[C:11]([CH:15]=2)[C:12]([OH:14])=O)=[CH:5][NH:4][N:3]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.[CH:22]([N:25](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.CN>CN(C=O)C.C1COCC1>[CH3:22][NH:25][C:12](=[O:14])[C:11]1[CH:15]=[C:7]([C:6]2[C:2](=[O:1])[N:3]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[NH:4][CH:5]=2)[CH:8]=[N:9][CH:10]=1
Reactant: O=C(O)c1cncc(-c2c[nH]n(-c3ccccn3)c2=O)c1
Reactant: CCN(C(C)C)C(C)C
Agent: CN
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CNC(=O)c1cncc(-c2c[nH]n(-c3ccccn3)c2=O)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
45.0 mg (159 μmol) of the compound from Example 44 are dissolved in 1 ml DMF, 1.9 mg (16 μmol) 4-N,N-dimethylaminopyridine, 24.7 mg (191 μmol) N,N-diisopropylethylamine and 100 mg (191 μmol) (benzotriazol-1-yloxy)-tripyrrolidinophosphonium hexafluorophosphate are added and the mixture is stirred at RT for 15 min. 120 μl (239 μmol) of a 2 M solution of methylamine in THF are added and the mixture is stirred overnight at RT. To bring the conversion to completion, a further 120 μl (239 μmol) of the 2 M solution of methylamine in THF are added and the mixture is stirred again overnight at RT. The reaction mixture is purified directly by means of preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.Br[CH2:10][C:11]([O:13][CH3:14])=[O:12].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:7]=1
Reactant: Oc1ccc(Br)cn1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)Cn1cc(Br)ccc1=O
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A mixture of 5-bromopyridin-2-ol (100 mg, 0.57 mmol), methyl 2-bromoacetate (168 mg, 1.1 mmol) and potassium carbonate (238 mg, 1.7 mmol) in acetone (5 mL) was stirred at 60° C. for 3 h. The solution was allowed to cool to room temperature, filtered and the filter cake was washed with acetone (5 mL×2). The filtrate was collected and concentrated under reduced pressure to give the crude product, which was purified by silica gel column chromatography (PE: EA=15:1) to afford the title compound: LC/MS m/z=246.1 [M+H]+
Reaction SMILES: [I-].[Na+].C[Si](Cl)(C)C.[C:8]([C:12]1[CH:31]=[CH:30][CH:29]=[CH:28][C:13]=1[O:14][C:15]1[N:16]=[N:17][C:18]([Cl:27])=[C:19]([Si](C)(C)C)[C:20]=1[O:21][CH3:22])([CH3:11])([CH3:10])[CH3:9]>C(#N)C>[C:8]([C:12]1[CH:31]=[CH:30][CH:29]=[CH:28][C:13]=1[O:14][C:15]1[N:16]=[N:17][C:18]([Cl:27])=[CH:19][C:20]=1[O:21][CH3:22])([CH3:11])([CH3:9])[CH3:10]
Reactant: COc1c(Oc2ccccc2C(C)(C)C)nnc(Cl)c1[Si](C)(C)C
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: COc1cc(Cl)nnc1Oc1ccccc1C(C)(C)C

Procedure:
0.17 g (1.1 mmol) of sodium iodide, 0.14 mL (1.1 mmol) of trimethylsilyl chloride and acetonitrile (3.5 mL) were mixed, and to the mixture was added with stirring 340 mg (0.932 mmol) of 3-(2-tert-butylphenoxy)-6-chloro-4-methoxy-5-(trimethylsilyl)pyridazine obtained in (1), and the resulting mixture was stirred at room temperature for 1 hour and 35 minutes. The reaction mixture was poured into a saturated aqueous sodium sulfite solution, and ice-cold diluted hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate, the organic layers were combined and washed with brine. The solvent was removed, and the residue was purified by silica gel column chromatography to obtain 275 mg (0.783 mmol, Yield: 84.0%) of 3-(2-tert-butylphenoxy)-6-chloro-5-(trimethylsilyl)-4-pyridazinol (Compound No. 2405).
Reaction SMILES: [OH:1][CH:2]([CH2:20][OH:21])[CH2:3][NH:4][C:5]([C:7]1[CH:12]=[C:11]([CH:13]([OH:16])[CH2:14][OH:15])[CH:10]=[C:9]([N+:17]([O-])=O)[CH:8]=1)=[O:6]>CO.O.[Pd]>[OH:1][CH:2]([CH2:20][OH:21])[CH2:3][NH:4][C:5]([C:7]1[CH:8]=[C:9]([CH:10]=[C:11]([CH:13]([OH:16])[CH2:14][OH:15])[CH:12]=1)[NH2:17])=[O:6]
Reactant: O=C(NCC(O)CO)c1cc(C(O)CO)cc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: O
Solvent: CO
Product: Nc1cc(C(=O)NCC(O)CO)cc(C(O)CO)c1

Procedure:
1-(2,3-Dihydroxypropylaminocarbonyl)-3-nitro-5-(1,2-dihydroxyethyl)benzene (0.40 g, 1.32 mmol) was dissolved in a mixture of methanol (40 ml) and water (20 ml). The solution was hydrogenated at 60 psi using a Pd/C catalyst (10%, 50 mg). The solution was filtered through celite and the solvents were removed by evaporation. The product was >95% pure by HPLC analysis and was used without further purification.
Reaction SMILES: Br[C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[NH4+:10].[OH-]>>[Br:8][C:6]1[N:7]=[C:2]([NH2:10])[C:3]([Cl:9])=[N:4][CH:5]=1
Reactant: [NH4+]
Reactant: Clc1ncc(Br)nc1Br
Agent: [OH-]
Product: Nc1nc(Br)cnc1Cl
Temperature: 100 °C
Reaction time: 8 h
Yield: 66 %

Procedure:
Into a 250 mL sealed tube was placed compound 90d (50.0 g, 184 mmol) and NH4OH (150 mL). The resulting mixture was stirred overnight at 100° C. Upon cooling, a solid was collected by filtration and dried in an oven under reduced pressure to obtain the compound 90e as a grey solid (28.0 g, 66% yield), which was used in next step without further purification.