Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:10][CH3:11])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].N1C=CC=CC=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C(Cl)(Cl)Cl>[CH3:11][O:10][C:1](=[O:9])[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][S:26]([C:23]1[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=1)(=[O:28])=[O:27]
Reactant: COC(=O)c1ccccc1N
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: COC(=O)c1ccccc1NS(=O)(=O)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 88.6 %

Procedure:
To a solution of 2.00 g (0.013 mol) of methyl anthranilate dissolved in 20 mL of chloroform was added 3.2 mL (0.039 mol) of pyridine followed by 2.733 g (0.013 mol) of p-methoxybenzenesulfonyl chloride. The reaction mixture was stirred at room temperature for 5 h and then washed with 3N HCl and water. The organics were then dried over Na2SO4, filtered and concentrated in vacuo. The resulting white solid was washed with ether and dried in vacuo to provide 3.7 g (87%) of the desired sulfonamide. CI Mass Spec: 322 (M+H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:10]([CH3:31])([CH3:30])[CH2:11][C:12]([OH:29])([C:25]([F:28])([F:27])[F:26])[CH2:13][N:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:24])[CH:16]=[CH:15]2)[CH:7]=[CH:8][CH:9]=1)(=O)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:39][O:40][NH2:41]>CO>[OH:29][C:12]([C:25]([F:26])([F:27])[F:28])([CH2:11][C:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:1](=[N:41][O:40][CH3:39])[CH3:2])[CH:5]=1)([CH3:30])[CH3:31])[CH2:13][N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17](=[O:24])[CH:16]=[CH:15]1
Reactant: CC(=O)c1cccc(C(C)(C)CC(O)(Cn2ccc(=O)c3ccccc32)C(F)(F)F)c1
Reactant: CON
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CON=C(C)c1cccc(C(C)(C)CC(O)(Cn2ccc(=O)c3ccccc32)C(F)(F)F)c1
Temperature: 65 °C

Procedure:
A mixture of 1-[4-(3-acetylphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1-H-quinolin-4-one (55 mg, 0.12 mmol), potassium carbonate (72 mg, 0.52 mmol), and methoxyamine hydrochloride (42 mg, 0.51 mmol) in 1 mL of methanol was heated at 65° C. for 3 hours, cooled to room temperature, and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography to afford 1-(2-hydroxy-4-{3-[1-(methoxyimino)ethyl]phenyl}-4-methyl-2-trifluoromethyl-pentyl)-1H-quinolin-4-one. Yield: 48 mg.
Reaction SMILES: [NH2:1][C@@:2]1([CH2:9][C:10]#[C:11][C:12]2[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[N:13]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].N[C@H](C(O)=O)CS.CC(C)=O.CCOCC>CC#N.O.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH3:7][N:4]1[CH2:5][CH2:6][C@:2]2([N:1]=[C:11]([C:12]3[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)[N:13]=3)[CH2:10][CH2:9]2)[C:3]1=[O:8]
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C#CC[C@]2(N)CCN(C)C2=O)n1
Agent: [Ag+]
Agent: N[C@@H](CS)C(=O)O
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CC#N
Solvent: CCOCC
Solvent: CC(C)=O
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C2=N[C@@]3(CC2)CCN(C)C3=O)n1
Temperature: 80 °C
Reaction time: 0.08 h
Yield: 69.4 %

Procedure:
Silver trifluoromethanesulphonate (9.39 g, 36.56 mmol) was added in a single batch to a solution of (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (which may be prepared as described in Description 14a) (71 g, 182.81 mmol) in MeCN (1000 mL) and the reaction was heated at 80° C. for 22 hours. The solvent was evaporated and the residue dissolved in DCM (1000 mL). Saturated NaHCO3 (500 ml) and water (500 ml) were added and the mixture shaken. The phases were separated and the organic layer treated with a solution of cysteine (100 g, 825.35 mmol) in water (1500 ml). This mixture was stirred vigorously for 30 minutes. The mixture was filtered through a pad of celite, and the celite washed with DCM (2×100 ml). The phases were separated and the organic layer placed in a large beaker. To this was added a solution of cysteine (50 g, 412.68 mmol) in water (500 ml) and the mixture was stirred for a further 30 minutes. The phases were separated and the organic layer was washed with a mixture of sat. brine (500 ml) and water (500 ml). The organic layer was dried (MgSO4) and the solvent evaporated to afford a dark brown foam. To the foam was added acetone (50 ml) and almost immediately a thick precipitate formed. This was swirled for about 5 minutes prior to slow addition of Et2O (150 ml) over approx. 10 minutes. After addition, the suspension was left to stand for 30 minutes. The solid was filtered off and washed with ether (3×30 ml) to afford the title material as a light brown solid (D15a) (49.24 g), pure by NMR and consistent with that produced by Method 1;
Reaction SMILES: CON(C)[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Br:24])[N:19]=2)[CH:7]=1)=[O:5]>C1COCC1.CC1C([Mg]Br)=NC=CC=1>[Br:24][C:20]1[N:19]=[C:18]([CH2:17][N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15](=[O:16])[C:6]([C:4]([C:7]3[C:6]([CH3:4])=[CH:15][CH:14]=[CH:9][N:8]=3)=[O:5])=[CH:7]2)[CH:23]=[CH:22][CH:21]=1
Reactant: CON(C)C(=O)c1cn(Cc2cccc(Br)n2)c2ccccc2c1=O
Agent: Cc1cccnc1[Mg]Br
Solvent: C1CCOC1
Product: Cc1cccnc1C(=O)c1cn(Cc2cccc(Br)n2)c2ccccc2c1=O

Procedure:
Experimental conditions analogous to those described for Step 6 of Example 60 from 90 mg (0.22 mmol) of 1-(6-bromo-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid methoxy-methyl-amide in 1 mL THF and 1.96 mL 0.25M 3-methyl-2-pyridylmagnesium bromide. Yield: 22 mg of a white solid. LC-MSD, m/z for C22H16BrN3O2 [M+H]+=434.0, 436.0; HPLC retention time: 1.8 min.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-])=O)=[CH:4][CH:3]=1>CO.[Ni]>[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([NH2:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc([N+](=O)[O-])c(N)n1
Agent: [Ni]
Solvent: CO
Product: Cc1ccc(N)c(N)n1

Procedure:
A mixture of 6-methyl-3-nitro-2-pyridinamine (3 g, 19.8 mmol) and Raney Ni (1 g) in MeOH (150 ml) was stirred in an autoclave filled with H2 (50 psi) at 0° C. for 2 hours. When TLC showed the reaction was completed, the mixture was filtered, and the filtrate was concentrated to give 6-methyl-2,3-pyridinediamine.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2].Br[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.BrCC(OCC)=O.[Zn]>[NH2:2][C:1]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1)=[CH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]
Reactant: CCOC(=O)CBr
Reactant: N#Cc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Zn]
Solvent: C1CCOC1
Product: CCOC(=O)C=C(N)c1cccnc1
Reaction time: 0.83 h
Yield: 78.4 %

Procedure:
In an atmosphere of argon, activated zinc powder (4.88 g, 0.07 g atom) was suspended in anhydrous tetrahydrofuran (THF) (25.0 ml) to which was subsequently added dropwise several drops of ethyl bromoacetate while heating under reflux. When color of the reaction solution became green, 3-cyanopyridine (1.59 g, 15.0 mmol) was added to the solution, ethyl bromoacetate (6.0 ml, 51.4 mmol) was added dropwise thereto spending 50 minutes and then the mixture was heated under reflux for 15 minutes. After cooling, the reaction solution was diluted with THF, mixed with 50% potassium carbonate aqueous solution (15.0 ml) and then stirred for 30 minutes. After standing, the organic layer was collected and extracted three times with THF in the same manner and then the thus obtained organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by a silica gel column chromatography (ethyl acetate:hexane=2:1-4:1) to obtain the title compound (2.26 g, 72.3%) as pale yellow oil.
Reaction SMILES: O[C:2]1([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=2)[CH2:5][O:4][CH2:3]1.C(N(S(F)(F)[F:20])CC)C.[OH-].[Na+]>ClCCl.O>[F:20][C:2]1([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=2)[CH2:5][O:4][CH2:3]1
Reactant: CCN(CC)S(F)(F)F
Reactant: N#Cc1ccc(C2(O)COC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: N#Cc1ccc(C2(F)COC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 4-(3-hydroxyoxetan-3-yl)benzonitrile (Step 1, 600 mg, 3.43 mmol) in dichloromethane (55 mL) was added dropwise N-ethyl-N-(trifluoro-λ4-sulfanyl)ethanamine (662 mg, 4.11 mmol, dissolved in 5 mL dichloromethane) at a temperature of −78° C. After 30 minutes at this temperature, the reaction mixture was rapidly warmed to −20° C. by the aid of a water/ice bath for no longer than 30 seconds whereupon NaOH (1N aq., 20 mL) was added and the reaction mixture was allowed to warm to rt. The mixture was diluted with water (150 mL) and extracted with diethyl ether (3×50 mL). The organic extract was dried with anhydrous magnesium sulfate and filtered. After evaporation of the solvent, the crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 8:1) to afford the title compound in pure form (495 mg, 82%): 1H NMR (400 MHz, CDCl3) δ 7.76 (d, 2H), 7.73 (d, 2H), 5.15 (dd, 2H), 4.81 (dd, 2H); ES-MS m/z 178 (MH)+; HPLC RT (Method F) 1.59 min.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:10][CH2:11][CH3:12])[C:5]([O:7]CC)=O)[CH3:2].[Si:13]([O:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[CH2:24][Mg]Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[Cl-].[NH4+]>C1COCC1>[Si:13]([O:20][C:21]1[CH:22]=[C:23]([CH2:24][C:5](=[O:7])[CH:4]([O:3][CH2:1][CH3:2])[O:10][CH2:11][CH3:12])[CH:27]=[CH:28][CH:29]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15]
Reactant: CCOC(=O)C(OCC)OCC
Reactant: CC(C)(C)[Si](C)(C)Oc1cccc(C[Mg]Cl)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOC(OCC)C(=O)Cc1cccc(O[Si](C)(C)C(C)(C)C)c1
Temperature: -78 °C

Procedure:
Under an argon atmosphere, to a solution of ethyl diethoxyacetate (1.80 mL, 10.1 mmol) in THF (20 mL) was added slowly a THF solution of (103) prepared above at −78° C. After stirring at −78° C. for an hour, to this was added 20% aqueous solution of ammonium chloride (30 mL) and the product was extracted with ethyl acetate (×3). The organic layer was sequentially washed with water (×1) and saturated brine (×1), and dried over anhydrous sodium sulfate. After filtration, the mixture was concentrated under reduced pressure and the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=10/1) to give 3-[3-(tert-butyldimethylsilyloxy]phenyl]-1,1-diethoxypropan-2-one (104) as a colorless oily substance (1.90 g, 5.39 mmol, 53.9%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1)(=[O:10])=[O:9].Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.CCCCCC.CCOC(C)=O>O1CCOCC1>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([N:11]2[C:23](=[O:25])[NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[S:8]2(=[O:10])=[O:9])[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]
Reactant: COc1ccc(NS(=O)(=O)c2ccccc2N)cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1COCCO1
Product: COc1ccc(N2C(=O)Nc3ccccc3S2(=O)=O)cc1OC
Yield: 46.2 %

Procedure:
A mixture of 2-amino-N-(3,4-dimethoxyphenyl)benzenesulfonamide (0.8 g, 2.6 mmol) and triphosgene (0.99 g, 3.4 mmol) in anhydrous 1,4-dioxane was heated in a sealed tube at 100° C. overnight with TLC monitoring (hexane:EtOAc, 1:1). After concentration in vacuo H2O (30 mL) was added and the mixture was extracted with EtOAc (3×100 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by gradient flash chromatography, eluting with 20-25% EtOAc in hexane yielded the title compound (0.4 g, 1.20 mmol).
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9](Cl)[CH:8]=[C:7]([NH:12][CH2:13][CH2:14][OH:15])[C:6]=1[N+:16]([O-:18])=[O:17].[CH3:19][O-:20].[Na+]>CO>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9]([O:20][CH3:19])[CH:8]=[C:7]([NH:12][CH2:13][CH2:14][OH:15])[C:6]=1[N+:16]([O-:18])=[O:17]
Reactant: O=[N+]([O-])c1c(NCCO)cc(Cl)cc1NCCO
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(NCCO)c([N+](=O)[O-])c(NCCO)c1

Procedure:
0.09 mole (25 g) of 2-(β-hydroxyethyl)amino-6-(β-hydroxyethyl)amino-4-chloronitrobenzene in 100 ml of a 25% sodium methylate solution in methanol was heated over a boiling water bath. After heating for 1 hour 30 minutes the desired product was precipitated out of the reaction medium by adding 250 g of ice water. After filtering and hot drying under vacuum in the presence of P2O5, the desired product was recrystallized from 96° ethanol. It melted at 150° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[S:9]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10]1.C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[Cl:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:11]2[CH:12]=[CH:13][S:9][CH:10]=2)[N:3]=1
Reactant: Clc1cncc(Cl)n1
Reactant: OB(O)c1ccsc1
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: COCCOC
Product: Clc1cncc(-c2ccsc2)n1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
1,2-Dimethoxyethane (120 mL) was added to a mixture of tetrakis(triphenylphosphine)palladium (0) (0.87 g, 0.75 mmol) and 2,6-dichloropyrazine (2.43 g, 16.3 mmol). After 15 min of stirring at room temperature, thiophene-3-boronic acid (2.09 g, 16.3 mmol) followed by aqueous Na2CO3 (2 M; 25 mL) were added. The mixture was heated at reflux for 2 h [TLC monitoring by SiO2/n-hexane/ethyl acetate (85:15)]. The layers were separated and the light brownish water layer was extracted with ether (2×100 mL). The combined organic layers were dried (K2CO3), filtered and concentrated in vacuo. The brownish oil obtained was purified by silica gel chromatography (18×5 cm) eluting with n-hexane/ethyl acetate (85:15). This furnished 1.46 g (45%) of the title compound as an off-white solid. HRMS m/z calcd for C8H5ClN2S (M)+ 195.9862, found 195.9868. Anal. (C8H5ClN2S) C, H, N.
Reaction SMILES: C(SCC1[C:15]2[C:10](=[CH:11][CH:12]=[C:13](C3C=CC=CC=3)[CH:14]=2)[NH:9]C(C)(C)C=1)C=C.Br[CH2:25][C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[O:42][CH3:43])[CH:34]=2)[NH:29][C:28]([CH3:45])([CH3:44])[CH:27]=1.C(=O)([O-])[O-].[K+].[K+].C(S)C=C>>[CH3:43][O:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[C:33]1[CH:34]=[C:35]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH3:45])([CH3:44])[CH:27]=[C:26]2[CH2:25][NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: COc1ccccc1-c1ccc2c(c1)C(CBr)=CC(C)(C)N2
Reactant: C=CCSCC1=CC(C)(C)Nc2ccc(-c3ccccc3)cc21
Agent: C=CCS
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccccc1-c1ccc2c(c1)C(CNc1ccccc1)=CC(C)(C)N2

Procedure:
4-Allylsulfanylmethyl-2,2-dimethyl-6-phenyl-1,2-dihydroquinoline 40 mg of 4-bromomethyl-6-(2-methoxyphenyl)-2,2-dimethyl-1,2-dihydroquinoline, 46 mg of potassium carbonate, and 44 μL of allyl mercaptan reacted to give 5 mg of the title compound as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][Si](C)(C)C)=[CH:8][CH2:7][CH2:6]2.F[B-](F)(F)F.[F:23][C:24]([F:39])([F:38])[S+]1C2C=CC=CC=2C2C=CC=CC1=2>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.C1C=CC([Sn-](F)(F)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH:8]([C:24]([F:39])([F:38])[F:23])[CH2:7][CH2:6]2
Reactant: FC(F)(F)[s+]1c2ccccc2c2ccccc21
Reactant: COc1ccc2c(c1)CCC=C2O[Si](C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)CCC(C(F)(F)F)C2=O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of (6-methoxy-3,4-dihydronaphthalen-1-yloxy)-trimethylsilane (3.00 g, from step A) and 5-trifluoromethyldibenzothiophenium tetrafluoroborate (5.6 g, 16.5 mmol) in DMF (20 mL) is added slowly tetrabutylammonium difluorotriphenylstannate (7.0 g, 11.1 mmol) in DMF (40 mL) by a dropping funnel. After the addition is finished, the suspension is stirred at RT for 72 h. DMF is then removed under vacuum. Water and EtOAc are added. The organic layer is dried with MgSO4, concentrated and purified to give the title compound as a light yellow oil: 1H NMR (CDCl3) δ 2.24-2.31 (m, 1H), 2.44-2.50 (m, 1H), 3.01-3.07 (m, 2H), 3.20-3.25 (m, 1H), 3.87 (s, 3H), 6.70 (d, J=2.5 Hz, 1H), 6.86 (dd, J=2.52, 9 Hz, 1H), 8.04 (d, J=9 Hz, 1H).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1C[O:14]CC1.[CH2:16]([O:18][C:19](=[O:37])[CH2:20][C:21]1[C:22]([CH3:36])=[N:23][C:24]2[N:25]([N:28]=[C:29]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:30]=2)[C:26]=1[I:27])[CH3:17].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[CH2:16]([O:18][C:19](=[O:37])[CH:20]([C:21]1[C:22]([CH3:36])=[N:23][C:24]2[N:25]([N:28]=[C:29]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:30]=2)[C:26]=1[I:27])[OH:14])[CH3:17]
Reactant: CCOC(=O)Cc1c(C)nc2cc(C(=O)OCC)nn2c1I
Reactant: C1CCOC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Agent: [K+]
Product: CCOC(=O)c1cc2nc(C)c(C(O)C(=O)OCC)c(I)n2n1
Reaction time: 0.5 h
Yield: 62.2 %

Procedure:
To a stirred solution of 0.9M KHMDS/THF (39.1 mL, 35.2 mmol) in THF (100 mL) at −78° C. was added a THF (50 mL) solution of ethyl 6-(2-ethoxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (11.3 g, 27.1 mmol) over the course of 5 min. After 30 min, a THF (50 mL) solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (9.20 g, 35.2 mmol) was added to the red reaction mixture and stirring was continued for an additional 30 min at −78° C. Then, the resulting orange reaction mixture was quenched with sat. aq. NH4Cl (50 mL), diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo to give a solid. This solid was triturated with small amount of ethyl acetate and solids were filtered, washed with hexanes and dried under high vacuum to afford ethyl 6-(2-ethoxy-1-hydroxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (7.3 g, 16.85 mmol, 62.2% yield) as light yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.33 (s, 1H), 5.75 (d, J=2.1 Hz, 1H), 4.52 (qd, J=7.1, 1.2 Hz, 2H), 4.37-4.30 (m, 2H), 3.57 (d, J=2.4 Hz, 1H), 2.63 (s, 3H), 1.48 (t, J=7.2 Hz, 3H), 1.27 (t, J=7.0 Hz, 3H). LCMS (M+H)=434.1.
Reaction SMILES: C[N:2]([CH:4]=[N:5][C:6]1[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[CH2:8][C:7]=1[C:14]([O:16]C)=O)C>N.CO>[CH3:12][C:9]1([CH3:13])[CH2:10][CH2:11][C:6]2[N:5]=[CH:4][NH:2][C:14](=[O:16])[C:7]=2[CH2:8]1
Reactant: COC(=O)C1=C(N=CN(C)C)CCC(C)(C)C1
Agent: N
Solvent: CO
Product: CC1(C)CCc2nc[nH]c(=O)c2C1
Yield: 0.1 %

Procedure:
A solution of methyl 2-((dimethylamino)methyleneamino)-5,5-dimethylcyclohex-1-enecarboxylate (9.5 g, 40 mol) in 7.0M ammonia in methanol (35 mL) was stirred at 25° C. for 90 minutes then concentrated to an oil. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes, 1:8) to give 6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one (6.41 g, 90% yield) as a white solid. 1H NMR (400 MHz, d6-DMSO): 7.96 (s, 1H), 2.52 (t, 2H), 2.14 (s, 2H), 1.48 (t, 2H), 0.93 (s, 6H); MS (EI) for C10H14N2O: 179 (MH+).
Reaction SMILES: C([O:14][C:15]1[C:24]2[N:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:18]([C:25](O)=[O:26])=[C:17]2[CH2:28][N:29]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[C:30](=[O:31])[C:16]=12)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:40][NH:41][CH3:42].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[CH3:40][N:41]([CH3:42])[C:25]([C:18]1[C:19]2[CH:20]=[CH:21][CH:22]=[N:23][C:24]=2[C:15]([OH:14])=[C:16]2[C:30](=[O:31])[N:29]([CH2:32][C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[CH2:28][C:17]=12)=[O:26]
Reactant: CNC
Reactant: O=C(O)c1c2c(c(OC(c3ccccc3)c3ccccc3)c3ncccc13)C(=O)N(Cc1ccc(F)cc1)C2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)C(=O)c1c2c(c(O)c3ncccc13)C(=O)N(Cc1ccc(F)cc1)C2
Temperature: 25 °C
Reaction time: 15 h
Yield: 95.9 %

Procedure:
9-Benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinoline-5-carboxylic acid 213 (0.02 g, 0.0386 mmol) was dissolved in 0.3 mL of dimethylformamide. To this was added dimethylamine (2M in THF) (0.0386 mL, 0.0772 mmol), diisopropylethylamine (0.027 mL, 0.1544 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.03 g, 0.0772 mmol) and stirred at room temperature. After 15 hours, starting material was consumed. Purified by reverse phase HPLC (0.1% TFA, H2O/ACN) to give 7-(4-fluoro-benzyl)-9-hydroxy-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinoline-5-carboxylic acid dimethylamide 321 (0.014 g, 0.037 mmol, 97%.) 1H NMR (CDCl3) o9.07 (dd, 1H), 8.18 (d, 1H), 7.65 (dd, 3H), 7.03(dd, 2H), 4.79 (dd, 2H), 4.53 (d, J=17 Hz, 1H), 4.25 (d, J=17 Hz, 1H), 3.24 (s, 3H), 3.21 (s, 3H.) MS: 380 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH2:12])=[C:4](I)[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]#[CH:22]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH2:12])=[C:4]([C:22]#[C:21][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[Cl:14])[CH:3]=1
Reactant: Nc1c(I)cc(Cl)cc1C(F)(F)F
Reactant: C#Cc1ccccc1Cl
Product: Nc1c(C#Cc2ccccc2Cl)cc(Cl)cc1C(F)(F)F

Procedure:
The title compound was prepared in analogy to example 10 step A from 4-chloro-2-iodo-6-trifluoromethyl-phenylamine (1.5 g, 4.67 mmol) and 1-chloro-2-ethynyl-benzene (766 mg, 5.6 mmol). Brown solid (1.05 g, 68%). LC-MS (ESI): 328 (M−H)−.
Reaction SMILES: [OH:1][C@H:2]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[CH:4]([CH2:5][CH2:6][C:7]3[C:8]4[C@:16]([CH3:24])([CH2:17][CH2:18][C:19]=32)[C@@H:11]([C@H:12]([CH3:15])[CH:13]=O)[CH2:10][CH:9]=4)[C:3]1([CH3:26])[CH3:25].[CH3:27][O:28][CH2:29][CH2:30][CH2:31][NH2:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:27][O:28][CH2:29][CH2:30][CH2:31][NH:32][CH2:15][C@H:12]([C@@H:11]1[C@:16]2([CH3:24])[C:8]([C:7]3[CH2:6][CH2:5][C@@H:4]4[C@:20]([C:19]=3[CH2:18][CH2:17]2)([CH3:23])[CH2:21][CH2:22][C@H:2]([OH:1])[C:3]4([CH3:26])[CH3:25])=[CH:9][CH2:10]1)[CH3:13]
Reactant: C[C@H](C=O)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)C1CC3
Reactant: COCCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: COCCCNC[C@@H](C)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3

Procedure:
(20S)-3β-hydroxy-4,4,20-trimethyl-pregna-8,14-dien-21-al was treated with 3-methoxypropylamine and sodium tris(acetoxy)borohydride as described in Example 1h). (20S)-20-[N-(3-methoxypropyl)aminomethyl]-4,4-dimethyl-5α-pregna-8,14-dien-3β-ol was isolated as a white solid.