Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=O)=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H]>[Pd].C(O)C>[CH3:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[NH:8][CH2:9][CH2:10]2
Reactant: O=Cc1ccc2c(c1)CCN2Cc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Cc1ccc2c(c1)CCN2
Reaction time: 8 h
Yield: 80.4 %

Procedure:
Into a 200 mλ atmospheric pressure hydrogenation apparatus equipped with a thermometer and a stirrer, 2.0 g (0.0084 mol) of 1-benzyl-5-formylindoline, 0.4 g of 5% 5 Pd/C and 100 mλ of ethanol were charged, and while introducing hydrogen under atmospheric pressure, a reaction was carried out at from 60 to 70° C. for 8 hours, and when the absorption of hydrogen ceased, the reaction was terminated. After termination of the reaction, the lo palladium catalyst (5% Pd/C) was collected by filtration, and ethanol was distilled off under reduced pressure to obtain a slightly red liquid. The obtained liquid was subjected to vacuum distillation to obtain 0.9 g of 5-methylindoline having a boiling point of 93° C./4 mmHg. The yield was 80.4% (based on the 1-benzyl-5-formylindoline).
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][OH:13])=[CH:8][CH:7]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:29]3[C:28]([N:30]4[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]4)=[N:27][CH:26]=[N:25][C:24]=3[S:23][CH:22]=2)=[CH:17][CH:16]=1>CC(O)C.CS(C)=O>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:29]3[C:28]([N:30]4[CH2:35][CH2:34][CH:33]([NH:36][CH2:3][CH:2]([OH:1])[CH2:4][O:5][C:6]5[CH:11]=[CH:10][C:9]([CH2:12][OH:13])=[CH:8][CH:7]=5)[CH2:32][CH2:31]4)=[N:27][CH:26]=[N:25][C:24]=3[S:23][CH:22]=2)=[CH:17][CH:16]=1
Reactant: NC1CCN(c2ncnc3scc(-c4ccc(F)cc4)c23)CC1
Reactant: OCc1ccc(OCC2CO2)cc1
Solvent: CC(C)O
Solvent: CS(C)=O
Product: OCc1ccc(OCC(O)CNC2CCN(c3ncnc4scc(-c5ccc(F)cc5)c34)CC2)cc1
Yield: 29 %

Procedure:
Synthesis followed SP6 (iPrOH:DMSO 1:1, 12 h), using 150 μmol (4-(oxiran-2-ylmethoxy)phenyl)methanol and 1-(5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl)piperidin-4-amine to give the title compound with 29% yield upon purification by prep. HPLC (reversed phase) and subsequent by prep. TLC (1 mm silica gel, PE/CH2Cl2/MeOH 4:6:1).
Reaction SMILES: [C:1]([OH:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].I[CH2:13][C:14]([OH:16])=[O:15]>C(O)C.O>[C:1]([S:8][CH2:13][C:14]([OH:16])=[O:15])(=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CI
Reactant: OC(=S)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)CSC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 97.8 %

Procedure:
To a purged stirring solution at 0° C. of (5.74 g, 41.6 mmoles) thiobenzoic acid in (100 mL) ethanol was added (27.8 mL, 3N, 83.2 mmoles) potassium hydroxide followed by (7.70 g, 41.6 mmoles) iodoacetic acid in (30 mL) ethanol. The solution stirred for 10 hours at room temperature under argon. The ethanol was rotavapped and the orange solid product was dissolved in (40 mL) water. The solution was acidified to pH 2.0 where an orange precipitate formed. This was filtered, washed with water, and dried in vacuo to give (7.98 g, 99% yield) benzoylmercaptoacetic acid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[CH3:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17]Cl)=[CH:15][CH:14]=1>>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:17][C:16]3[CH:19]=[CH:20][C:13]([O:12][CH3:11])=[CH:14][CH:15]=3)[CH:9]=[CH:10][C:3]=12
Reactant: COc1ccc(CCl)cc1
Reactant: Brc1ccnc2[nH]ccc12
Product: COc1ccc(Cn2ccc3c(Br)ccnc32)cc1

Procedure:
Reaction of 4-bromo-1H-pyrrolo[2,3-b]pyridine with 4-methoxybenzyl chloride following the method of Example 12 affords the title compound.
Reaction SMILES: Br[C:2]1[C:3]2[CH2:12][CH2:11][CH2:10][C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][C:19]=2B2OC(C)(C)C(C)(C)O2)[CH2:15][CH2:14]1.C([O-])([O-])=O.[K+].[K+].CC(=O)OCC>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CO>[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][C:19]=2[C:2]2[C:3]3[CH2:12][CH2:11][CH2:10][C:4]=3[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH2:14][CH2:15]1
Reactant: CC1(C)OB(c2cc(S(C)(=O)=O)ccc2OCC2CC2)OC1(C)C
Reactant: Cn1cc(Br)c2c(c1=O)CCC2
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: Cn1cc(-c2cc(S(C)(=O)=O)ccc2OCC2CC2)c2c(c1=O)CCC2
Temperature: 85 °C
Yield: 48.4 %

Procedure:
To a solution of the title compound of step 7 (60 mg, 0.26 mmol), the title compound of Example 90, step 1 (111.2 mg, 0.32 mmol) and K2CO3 (107 mg, 0.78 mmol) in dioxane (4 mL) and water (1 mL) was added Pd(dppf)Cl2 (6 mg) under N2. The mixture was heated at 85° C. overnight. EA extractive work up followed by prep-TLC (DCM/MeOH=25:1) gave the title compound (47 mg, 48%) as a yellow solid. 1H NMR (DMSO-d6, 300 MHz): δ 7.83 (dd, J=8.7, 2.7 Hz, 1H), 7.66 (d, J=2.9 Hz, 1H), 7.58 (s, 1H), 7.25 (d, J=8.7 Hz, 1H), 3.95 (d, J=6.9 Hz, 2H), 3.46 (s, 3H), 3.17 (s, 3H), 2.65-2.70 (m, 4H), 1.91-1.97 (m, 2H), 1.13-1.18 (m, 1H), 0.50-0.54 (m, 2H), 0.26-0.30 (m, 2H). LCMS: 374 (M+1)+
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1.II.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[F:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][CH:9]=[C:8]([CH3:11])[CH:7]=3)[N:1]=2)=[CH:15][CH:14]=1
Reactant: Cc1ccc(N)c(C(N)=O)c1
Reactant: O=Cc1ccc(F)cc1
Agent: II
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2nc(-c3ccc(F)cc3)[nH]c(=O)c2c1
Temperature: 80 °C
Reaction time: 16 h
Yield: 82.8 %

Procedure:
A mixture of 2-amino-5-methylbenzamide (1.0 g, 6.7 mmol), 4-fluorobenzaldehyde (0.83 g, 6.7 mmol), iodine (2.03 g, 8.0 mmol), and potassium carbonate (1.38 g, 10 mmol) in DMF (50 mL) was stirred at 80° C. for 16 hours. The reaction mixture was cooled to 20° C. and poured into icy water. The solid was collected by filtration, washed with water, and air dried to give 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.41 g, 83%). A solution of 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.4 g, 5.5 mmol), NBS (0.98 g, 5.6 mmol), and benzoyl peroxide (67.0 mg, 0.276 mmol) in AcOH (150 mL) and chloroform (150 mL) was stirred at 80° C. for 5 hours with light shedding on. The reaction mixture was cooled to 20° C. and concentrated using a rotary evaporator to yield the crude bromide. A solution of the above crude bromide in DMF (20 mL) and 1,4-dioxane (100 mL) was mixed with morpholine (10 mL) and stirred at 80° C. for 4 hours. The reaction was quenched by adding water (200 mL), extracted with dichloromethane (3×100 mL), and concentrated using a rotary evaporator. The residue was further purified by column (SiO2, Hexanes/EtOAc/MeOH=4:3:1) to yield 2-4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 48% over two steps). A solution of 2-(4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 2.62 mmol) in dichloromethane (100 mL) and MeOH (50 mL) was mixed with HCl in ether (8 mL, 16 mmol) and stirred for 1 hour. The reaction was concentrated using a rotary evaporator. The solid was rinsed with DCM (50 mL) and MeOH (5 mL), collected by filtration, washed with DCM-MeOH (10:1) to afford 2-(4-fluorophenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one (0.82 g, 76%) as an off-white solid; MS (ES) m/z: 340 (M+1); MP 321.8-323.3° C.
Reaction SMILES: [ClH:1].[OH:2][C:3]1[C:12]2[C:7](=[C:8]([NH:13][C@H:14]3[CH2:19][CH2:18][C@H:17]([NH:20]C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[CH:9]=[CH:10][CH:11]=2)[C:6]([CH3:28])=[CH:5][N:4]=1>>[ClH:1].[OH:2][C:3]1[C:12]2[C:7](=[C:8]([NH:13][C@H:14]3[CH2:15][CH2:16][C@H:17]([NH2:20])[CH2:18][CH2:19]3)[CH:9]=[CH:10][CH:11]=2)[C:6]([CH3:28])=[CH:5][N:4]=1
Reactant: Cc1cnc(O)c2cccc(N[C@H]3CC[C@H](NC(=O)OC(C)(C)C)CC3)c12
Agent: Cl
Product: Cc1cnc(O)c2cccc(N[C@H]3CC[C@H](N)CC3)c12

Procedure:
According to the method of Step A of this example, deprotection with concentrated hydrochloric acid was performed by using Intermediate 140 to obtain the title compound.
Reaction SMILES: Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:12][N:11]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(NC(C)C)(C)C.C[Si](C)(C)[C:32]#[C:33][C:34]1([CH3:38])[CH2:37][O:36][CH2:35]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.[Cu]I>[CH3:38][C:34]1([C:33]#[C:32][C:2]2[C:3]([O:8][CH:9]3[CH2:12][N:11]([C:13]4[CH:22]=[CH:21][C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]=4)[CH2:10]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:37][O:36][CH2:35]1
Reactant: CC1(C#C[Si](C)(C)C)COC1
Reactant: Clc1nccnc1OC1CN(c2ccc3ccccc3n2)C1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)NC(C)C
Product: CC1(C#Cc2nccnc2OC2CN(c3ccc4ccccc4n3)C2)COC1
Temperature: 85 °C
Yield: 12.1 %

Procedure:
Tetrakis(triphenylphosphine)palladium (288 mg, 0.249 mmol), copper(i) iodide (190 mg, 0.998 mmol) and 2-(3-(3-chloropyrazin-2-yloxy)azetidin-1-yl)quinoline (see PREPARATION P2.6; 312 mg, 0.998 mmol) were combined in a microwave vial which was degassed and backfilled with nitrogen (procedure was repeated three times). DMF (1663 μL) was added followed by diisopropylamine (2097 μL, 14.96 mmol) and trimethyl((3-methyloxetan-3-yl)ethynyl)silane (840 mg, 4.99 mmol). The tube was sealed and heated to 85° C. for 16 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with brine and water. The aqueous layer was back extracted with EtOAc (3×) and the combined organic phase was dried over Na2SO4. The solvent was removed under reduced pressure. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide 2-(3-(3-((3-methyloxetan-3-yl)ethynyl)pyrazin-2-yloxy)azetidin-1-yl)quinoline (45 mg, 0.121 mmol, 12.11% yield) as orange powder. 1H NMR (400 MHz, chloroform-d) δ ppm 1.76 (s, 3H) 4.28 (dd, J=9.88, 4.21 Hz, 2H) 4.47 (d, J=5.48 Hz, 2H) 4.67 (dd, J=9.59, 6.65 Hz, 2H) 4.97 (d, J=5.48 Hz, 2H) 5.52-5.62 (m, 1H) 6.63 (d, J=8.80 Hz, 1H) 7.21-7.41 (m, 2H) 7.45-7.65 (m, 1H) 7.76 (d, J=8.22 Hz, 1H) 7.90 (d, J=8.80 Hz, 1H) 8.03 (d, J=2.74 Hz, 1H) 8.17 (d, J=2.54 Hz, 1H). ESI (M+1) 373.1; calc for C22H20N4O2 372. (PDE10 IC50=0.0446 nM).
Reaction SMILES: C([N:8]1[C@H:22]2[C@H:11]([CH2:12][S:13][C@H:14]2[CH2:15][CH2:16][CH2:17][CH2:18][C:19](=[O:21])[OH:20])[N:10](CC2C=CC=CC=2)[C:9]1=[O:30])C1C=CC=CC=1.O.S(=O)(=O)(O)O.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[OH:21][C:19]([CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C@@H:22]2[C@@H:11]([NH:10][C:9]([NH:8]2)=[O:30])[CH2:12][S:13]1)=[O:20]
Reactant: O=C(O)CCCC[C@@H]1SC[C@H]2[C@@H]1N(Cc1ccccc1)C(=O)N2Cc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1C
Product: O=C(O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Reaction time: 3 h
Yield: 86.7 %

Procedure:
320 g of crude dibenzylbiotin (containing about 80% of pure dibenzylbiotin, 0.60 mol) are mixed with 125 g of water, and 500 g of sulfuric acid are carefully added with stirring at such a rate that the temperature of the batch does not exceed 115° C. Stirring is then continued at 115° C. for 3 hours. 2.5 l of xylene are added, and the mixture is then firstly neutralized using 5 l of 9% sodium hydroxide solution and then rendered alkaline. The aqueous phase is separated off. The xylene phase is extracted twice more with 0.5 1 of 9% sodium hydroxide solution in each case. The aqueous phase and the sodium hydroxide phases from the post-reactions are combined and adjusted to a pH of 6 at 80° C. using sulfuric acid. 12 g of activated carbon are added, the mixture is subjected to a polishing filtration, and the pH is slowly reduced to 1.5 using sulfuric acid. After the mixture has been cooled overnight, the precipitated biotin is filtered off with suction and dried, giving 128 g of biotin (content: about 99%, corresponding to 126 g of pure biotin=0.52 mol, 86% of theory).
Reaction SMILES: Cl.[C:2]([NH2:5])(=[NH:4])[CH3:3].[O-]CC.[Na+].[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH:25]([C:31](OCC)=[O:32])[C:26](OCC)=[O:27])=[CH:20][CH:19]=1)#[N:11].O1CCOCC1>C(O)C>[OH:32][C:31]1[N:4]=[C:2]([CH3:3])[NH:5][C:26](=[O:27])[C:25]=1[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([C:13]2[C:12]([C:10]#[N:11])=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:19][CH:20]=1
Reactant: CC(=N)N
Reactant: CCOC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OCC
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCO
Product: Cc1nc(O)c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)[nH]1
Yield: 40 %

Procedure:
To a solution of acetamidine hydrochloride (2.68 g) in ethanol (30 mL) were added sodium ethoxide (20% ethanol solution, 14.5 g) and then a solution of diethyl [(2′-cyanobiphenyl-4-yl)methyl]malonate in ethanol (30 mL)-1,4-dioxane (15 mL) at 0° C., and the reaction mixture was stirred at room temperature for 16 hr. The reaction mixture was concentrated, and the residue was adjusted to pH 5 with water (50 mL) and 50% aqueous acetic acid solution. The obtained crystallized product was collected by filtration and washed with water to give the title compound as colorless crystals (1.8 g, 40%).
Reaction SMILES: Cl.[C:2]1([CH2:7][NH2:8])[S:6][CH:5]=[CH:4][CH:3]=1.[S-:9][C:10]#[N:11].[NH4+]>BrC1C=CC=CC=1>[C:2]1([CH2:7][NH:8][C:10]([NH2:11])=[S:9])[S:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#C[S-]
Reactant: NCc1cccs1
Agent: Cl
Agent: [NH4+]
Solvent: Brc1ccccc1
Product: NC(=S)NCc1cccs1
Yield: 32.6 %

Procedure:
2-thenylamine hydrochloride (13.35 grams, 0.089 moles) and ammonium thiocyanate (7.4 grams, 0.089 moles) in 20 ml bromobenzene were heated to reflux temperature for 90 minutes. The reaction mixture was cooled and the filtered solids washed three times with water. Recrystallization from chloroform and drying over phosphorous pentoxide yielded 5.0 grams (33%) of N-thenylthiourea, m.p. 99°-101° C.
Reaction SMILES: [CH3:1][C:2]([CH3:22])([C@H:5]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH3:21])[N:16]=[CH:15]2)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]#[N:4].[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)C.[F:34][C:35]([F:41])([F:40])[CH2:36][C:37](O)=[O:38]>C1COCC1>[CH3:1][C:2]([CH3:22])([C@H:5]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH3:21])[N:16]=[CH:15]2)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[CH2:3][NH:4][C:37](=[O:38])[CH2:36][C:35]([F:41])([F:40])[F:34]
Reactant: O=C(O)CC(F)(F)F
Reactant: Cn1ncc2cc([C@H](c3ccccc3)C(C)(C)C#N)ccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cn1ncc2cc([C@H](c3ccccc3)C(C)(C)CNC(=O)CC(F)(F)F)ccc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 51.4 %

Procedure:
(b)(c) To a stirred solution of (S)-2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropanenitrile (54 mg, 0.193 mmol) in anhydrous THF (10 mL) was added 1.0M lithium aluminum hydride in diethyl ether (0.5 mL, 0.5 mmol) portionwise at RT under nitrogen. After stirring at RT for 3 hr, the mixture was carefully quenched with MeOH, poured into brine, extracted with ethyl acetate (2×100 mL), dried (MgSO4) and concentrated. The crude product was coupled with 3,3,3-trifluoropropanoic acid (29 mg, 0.226 mmol) using General Coupling Method A to give 40 mg (51% yield) of (S)—N-(2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropyl)-3,3,3-trifluoropropanamide. MS found: (M+H)+=404.
Reaction SMILES: C([O:8][N:9]1[C:18](=[O:19])[C:17]2[CH:20]=[C:21]([Br:29])[C:22]([N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[C:15]3[C:16]=2[C:11](=[CH:12][CH:13]=[CH:14]3)[C:10]1=[O:30])C1C=CC=CC=1.FC(F)(F)C([O-])=O.FC(F)(F)C([O-])=O.FC(F)(F)C([O-])=O.[B+3].C(OCC)C>C(O)(C(F)(F)F)=O>[Br:29][C:21]1[C:22]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:16]2=[C:17]([CH:20]=1)[C:18](=[O:19])[N:9]([OH:8])[C:10]3=[O:30]
Reactant: O=C1c2cccc3c(N4CCCCC4)c(Br)cc(c23)C(=O)N1OCc1ccccc1
Agent: O=C([O-])C(F)(F)F
Agent: [B+3]
Solvent: O=C(O)C(F)(F)F
Solvent: CCOCC
Product: O=C1c2cccc3c(N4CCCCC4)c(Br)cc(c23)C(=O)N1O
Temperature: 0 °C
Reaction time: 2 h
Yield: 27.6 %

Procedure:
To a solution of 2-benzyloxy-5-bromo-6-(piperidin-1-yl)-benzo[de]isoquinoline-1,3-dione (0.27 g, 0.58 mmol, from Example T1-A) in TFA (5 mL) at 0° C. was added a 1.0 M solution of boron tris(trifluoroacetate) in TFA (3 mL). The reaction was stirred at 0° C. for 2 hours. Ethyl ether was added forming a precipitate which was collected by filtration. The solid was taken up in chloroform, the organic layer washed with water, dried, filtered, and evaporated under reduced pressure to give 0.060 g of the title compound as the TFA salt, mp >250° C.
Reaction SMILES: [CH3:1][CH:2]1[CH:7]=[C:6]([CH3:8])[CH2:5][CH2:4][C:3]1([C:11]([CH3:13])=[CH2:12])[CH:9]=[O:10].Br[CH:15]([CH3:17])[CH3:16]>>[CH3:1][CH:2]1[CH:7]=[C:6]([CH3:8])[CH2:5][CH2:4][C:3]1([CH:9]([OH:10])[CH:15]([CH3:17])[CH3:16])[C:11]([CH3:13])=[CH2:12]
Reactant: C=C(C)C1(C=O)CCC(C)=CC1C
Reactant: CC(C)Br
Product: C=C(C)C1(C(O)C(C)C)CCC(C)=CC1C
Reaction time: 24 h
Yield: 72 %

Procedure:
To a mixture of Mg (1.2 g, 50 mmol), Li (0.35 g, 50 mmol) and 2,4-dimethyl-1-(prop-1-en-2-yl)cyclohex-3-enecarbaldehyde (8.9 g, 50 mmol) was added 2-bromopropane (7.5 g, 60 mmol). The mixture was stirred for 24 h under an argon atmosphere and was then poured on ice-cold sat. NH4Cl solution. The mixture was extracted with MTBE (3×50 ml). The combined org. phases were washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was distilled in a Kugelrohr oven to yield 8.0 g (72%) of a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[N:12][N:11]=[N:10]2)=[CH:5][C:4]=1[CH2:14][OH:15]>O1CCCC1.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[N:12][N:11]=[N:10]2)=[CH:5][C:4]=1[CH:14]=[O:15]
Reactant: COc1ccc(-n2cnnn2)cc1CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: COc1ccc(-n2cnnn2)cc1C=O
Reaction time: 0.5 h
Yield: 83.3 %

Procedure:
Active manganese dioxide (77 mg) was added to a stirred solution of 2-methoxy-5-(tetrazol-1-yl)phenylmethanol (40 mg) in tetrahydrofuran (1 ml). After 30 min the mixture was heated in an oil-bath at 70°. After a further 30 min, active manganese dioxide (67 mg) was added. After a further 1 h the mixture was allowed to cool and then filtered. The filtrate was evaporated to give the title compound as a yellow solid (33 mg); nmr, δ (d6 -DMSO), 4.4 (s,3H), 7.53 (d, 1H, J=ca 10 Hz), 8.12-8.23 (m, 2H), 10.12 (s, 1H), 10.40 (s, 1H).
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:33]([OH:35])[CH3:34])[C@@H:3]1[O:5][C@H:4]1[CH2:6][C@@H:7]1[C@@H:12]([OH:13])[C@@H:11]([OH:14])[C@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:19])[O:9][CH2:8]1.[O-2:36].[Ca+2:37]>C(OCC(C)C)(=O)C.O>[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[OH2:36].[OH2:5].[Ca+2:37]
Reactant: [O-2]
Reactant: C/C(=C\C(=O)OCCCCCCCCC(=O)O)C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Agent: [Ca+2]
Solvent: CC(=O)OCC(C)C
Solvent: O
Product: C/C(=C\C(=O)OCCCCCCCCC(=O)[O-])C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Temperature: 5 °C
Reaction time: 2 h
Yield: 62 %

Procedure:
Pseudomonic acid was dissolved in isobutyl acetate (130 ml). Calcium oxide (0.29 g) was suspended in water (32 ml) and added to the solution of pseudomonic acid. The mixture was stirred for 2 hours, and the phases were separated. The volume of the aqueous phase was reduced to 15 ml by vacuum distillation. The mixture was cooled to 5° C. After stirring for 2 hours, the crystalline product was filtered and washed with cooled water (5 ml). The product was dried in an air circulated oven at RT. Mupirocin calcium dihydrate (3.3 g, 62%) was obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=3[F:24])[C:17]([O:19]C)=[O:18])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:25][N:26]1[CH:30]=[C:29](B(O)O)[CH:28]=[N:27]1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:24][C:23]1[CH:22]=[CH:21][C:16]([C:17]([OH:19])=[O:18])=[CH:15][C:14]=1[NH:13][C:11]([C:8]1[N:5]2[CH:6]=[CH:7][C:2]([C:29]3[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=3)=[CH:3][C:4]2=[N:10][CH:9]=1)=[O:12]
Reactant: COC(=O)c1ccc(F)c(NC(=O)c2cnc3cc(Br)ccn23)c1
Reactant: Cn1cc(B(O)O)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Solvent: ClCCl
Product: Cn1cc(-c2ccn3c(C(=O)Nc4cc(C(=O)O)ccc4F)cnc3c2)cn1
Temperature: 100 °C

Procedure:
A mixture comprising methyl 3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-fluorobenzoate (Intermediate 1A) (5.41 g, 13.79 mmol), 1-methyl-1H-pyrazol-4-ylboronic acid (1.911 g, 15.17 mmol), Pd(dppf)Cl2.DCM (1.127 g, 1.379 mmol) and cesium carbonate (13.48 g, 41.4 mmol) in DME (100 ml) and water (10 ml) was heated at 100° C. for 4 hrs. 3 equivalents of sodium carbonate were added and the mixture was heated to 100° C. for 6 hrs. A further 3 equivalents of sodium carbonate were added and the reaction was heated at 100° C. overnight.
Reaction SMILES: [CH:1]([N:4]1[C:9](=[O:10])[CH:8]=[CH:7][C:6]([C:11](=[N:20]O)[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:13])=[N:5]1)([CH3:3])[CH3:2].[C:22](OC(=O)C)(=[O:24])[CH3:23].CC(O)=O>CCOC(C)=O.[Zn]>[CH:1]([N:4]1[C:9](=[O:10])[CH:8]=[CH:7][C:6]([CH:11]([NH:20][C:22](=[O:24])[CH3:23])[C:12](=[O:13])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)n1nc(C(=NO)C(=O)c2ccccc2)ccc1=O
Reactant: CC(=O)OC(C)=O
Agent: [Zn]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)NC(C(=O)c1ccccc1)c1ccc(=O)n(C(C)C)n1
Reaction time: 4 h

Procedure:
Zinc dust (1.57 g) was added in portions to a suspension of 1-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridazinyl)-2-phenyl-1,2-ethanedione 1-oxime (856 mg) in a mixture acetic anhydride (1.7 ml) and AcOH (10 ml) under ambient temperature and the mixture was stirred at the same temperature for 4 hours. An insoluble material was filtered off and a filtrate was concentrated under reduced pressure to give a residue. The residue was dissolved in EtOAc, washed with sat. aq. NaHCO3 solution, dried over MgSO4 and subjected to column chromatography on silica gel eluting with a mixture of MeOH and EtOAc (2:98 v/v) to give N-[1-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridazinyl)-2-oxo-2-phenylethyl]acetamide as a solid (724 mg).