Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([N+:14]([O-])=O)=[CH:12][CH:11]=[C:10]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:9]=1.[C:24]([C:26]1[O:30][C:29]([C:31](O)=[O:32])=[CH:28][CH:27]=1)#[N:25].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd].CO.ClCCl.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:10]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:11]=[CH:12][C:13]=1[NH:14][C:31]([C:29]1[O:30][C:26]([C:24]#[N:25])=[CH:27][CH:28]=1)=[O:32]
Reactant: CN1CCN(c2ccc([N+](=O)[O-])c(-c3ccccc3F)c2)CC1
Reactant: N#Cc1ccc(C(=O)O)o1
Agent: [Pd]
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CN1CCN(c2ccc(NC(=O)c3ccc(C#N)o3)c(-c3ccccc3F)c2)CC1
Yield: 76.7 %

Procedure:
The procedure of Example 9, step (c) was followed using 93.2 mg (0.225 mmol based on 76% purity) of 1-(2′-fluoro-6-nitro-biphenyl-3-yl)-4-methyl-piperazine (as prepared in the previous step), 46 mg of 10% palladium on carbon, 37.0 mg (0.270 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 35.3 μL (0.405 mmol) of oxalyl chloride, 5.0 μL of anh DMF, and 94.1 μL (0.540 mmol) of DIEA. Chromatography on a 5-g silica SPE column with 1-4% MeOH-dichloromethane afforded 69.8 mg (77%) of the title compound as a yellow resin. 1H-NMR (CDCl3; 400 MHz): δ 8.04 (d, 1H, J=9.0 Hz), 7.93 (br s, 1H), 7.434-7.48 (m, 1H), 7.37 (td, 1H, J=7.5, 1.8 Hz), 7.22-7.31 (m, 2H), 7.13, 7.18 (AB q, 2H, J=3.7 Hz), 7.02 (dd, 1H, J=9.0, 2.9 Hz), 6.88 (d, 1H, J=2.9 Hz), 3.24-3.27 (m, 4H), 2.57-2.60 (m, 4H), and 2.36 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C23H21FN4O2, 405.2 (M+H). found 405.2.
Reaction SMILES: [CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[CH2:21]([NH2:26])[CH2:22][CH:23]([CH3:25])[CH3:24].[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:26][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=1
Reactant: CC(C)CCN
Reactant: COc1cc(C=O)ccc1Oc1cnc(C(N)=O)cn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(CNCCC(C)C)ccc1Oc1cnc(C(N)=O)cn1
Reaction time: 8 h
Yield: 54.9 %

Procedure:
Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), isoamylamine (0.234 g, 2.69 mmol) and 3 Å molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 mmol) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes. Concentrate the fraction containing the product, and dissolve it in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2× 25 mL), dry it over Na2SO4, filter and concentrate to give the title compound (0.484 g, 54.9%): TOF MS ES+ 345.2 (M+H)+, HRMS calcd for C18H25N4O3 345.1927 (M+H)+, found 345.1938, time 0.38 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=10.1 min, 95.4% purity.
Reaction SMILES: [C-:1]#[N:2].[K+].C=O.[C:6]([O:13][C:14](OC(C)(C)C)=O)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]>CO>[C:6](=[O:7])([O:13][CH2:14][C:1]#[N:2])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: [C-]#N
Agent: C=O
Agent: [K+]
Solvent: CO
Product: CC(C)(C)OC(=O)OCC#N
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of potassium cyanide (600 g, 9.22 mol) in methanol (10 L) was added formaldehyde (38% solution in water, 1457 g, 18 mol) dropwise at 0° C. After 1 hour, di-tert-butyl dicarbonate (3018 g, 13.83 mol) was added batchwise at 0° C. The reaction mixture was allowed to warm to ambient temperature. After 4 hours, the reaction mixture was quenched with water (2 L) and extracted with ethyl acetate (4×2 L). The organics were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford tert-butyl cyanomethyl carbonate. The product was used without further purification.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([O:27][C:28]1[CH:29]=[C:30]([C:34]2[N:39]=[CH:38][C:37]([C:40]([OH:42])=O)=[CH:36][N:35]=2)[CH:31]=[CH:32][CH:33]=1)[CH3:26].CCN(C(C)C)C(C)C.[F:52][C:53]([F:66])([F:65])[C:54]1[NH:55][C:56]2[C:61]([CH:62]=1)=[CH:60][C:59]([CH2:63][NH2:64])=[CH:58][CH:57]=2>CN(C=O)C>[CH2:25]([O:27][C:28]1[CH:29]=[C:30]([C:34]2[N:35]=[CH:36][C:37]([C:40]([NH:64][CH2:63][C:59]3[CH:60]=[C:61]4[C:56](=[CH:57][CH:58]=3)[NH:55][C:54]([C:53]([F:66])([F:52])[F:65])=[CH:62]4)=[O:42])=[CH:38][N:39]=2)[CH:31]=[CH:32][CH:33]=1)[CH3:26]
Reactant: NCc1ccc2[nH]c(C(F)(F)F)cc2c1
Reactant: CCOc1cccc(-c2ncc(C(=O)O)cn2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOc1cccc(-c2ncc(C(=O)NCc3ccc4[nH]c(C(F)(F)F)cc4c3)cn2)c1
Reaction time: 24 h
Yield: 45.4 %

Procedure:
To a stirred solution of HATU (30.3 mg, 0.080 mmol) in DMF (1 ml) was added 2-[3-(ethyloxy)phenyl]-5-pyrimidinecarboxylic acid (Intermediate 7, 10 mg, 0.041 mmol) in DMF (0.5 ml), followed by DIPEA (0.021 ml, 0.120 mmol) and finally {[2-(trifluoromethyl)-1H-indol-5-yl]methyl}amine (Intermediate 4, 10 mg, 0.040 mmol) in DMF (1 ml). The solution was stirred for 24 hrs then DMF was removed using a rotary evaporator. DCM and sodium bicarbonate solution were then added to the residue. The mixture was poured through a phase separation cartridge, the organic layer evaporated to dryness and purified using MDAP to give the title compound as a yellow solid (8 mg);
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[C:6](=[N:7]O)[CH2:5][N:4]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[C:3]1=[O:17]>CO.[Ni]>[NH2:7][CH:6]1[CH2:5][N:4]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[C:3](=[O:17])[C:2]1([CH3:1])[CH3:18]
Reactant: C[C@H](c1ccccc1)N1CC(=NO)C(C)(C)C1=O
Agent: [Ni]
Solvent: CO
Product: C[C@H](c1ccccc1)N1CC(N)C(C)(C)C1=O
Reaction time: 16 h
Yield: 123.6 %

Procedure:
To a solution of 8.75 g of 3,3-dimethyl-4-hydroxyimino-1-[1-(R)-phenylethyl]-pyrrolidin-2-one in 300 ml of methanol there was added 20 ml of Raney-nickel, and reduction was carried out under a hydrogen atmosphere at room temperature for 16 hr (H2 pressure: 1 atm). The catalyst was removed by filtration and the solvent of the filtrate was removed under reduced pressure. The residue was purified through column chromatography using a column filled with 300 g of silica gel. From a fraction eluted with a mixture of methanol and chloroform(1:30, v/v), 3.75 g of the less polar isomer of the titled compound was obtained along with 10.2 g of a mixture of the less polar and more polar titled compound.
Reaction SMILES: [OH:1][N:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]([NH:5][C:6]1[S:10][N:9]=[N:8][CH:7]=1)=[O:4].[CH3:17][N:18]=[C:19]=[O:20]>C(N(CC)CC)C>[CH3:17][NH:18][C:19]([O:1][N:2]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:3]([NH:5][C:6]1[S:10][N:9]=[N:8][CH:7]=1)=[O:4])=[O:20]
Reactant: CN=C=O
Reactant: O=C(Nc1cnns1)N(O)c1ccccc1
Solvent: CCN(CC)CC
Product: CNC(=O)ON(C(=O)Nc1cnns1)c1ccccc1
Reaction time: 0.17 h

Procedure:
4.72 g (0.02 mole) 1-hydroxy-1-phenyl-3-(1,2,3-thiadiazole-5-yl)-urea were suspended in 40 ml tetrahydrafuran and then reacted with 1.19 ml (0.02 mole) methylisocyanate. After addition of 3 drops of triethylamine there is obtained a clear solution and after a further 10 minutes crystals already begin to separate out. The reaction mixture is allowed to stand at room temperature. Thereafter the crystals are separated off and digested with diisopropylether.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][C:11]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)=[C:12]([C:14](O)=[O:15])[N:13]=1.O.OC1C2N=N[NH:29]C=2C=CC=1.N.O1CCOCC1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][C:11]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)=[C:12]([C:14]([NH2:29])=[O:15])[N:13]=1
Reactant: Oc1cccc2[nH]nnc12
Reactant: O=C(O)c1nc(-c2c(F)cccc2F)oc1-c1cccs1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: N
Solvent: O
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: NC(=O)c1nc(-c2c(F)cccc2F)oc1-c1cccs1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 4 %

Procedure:
To a solution of 2-(2,6-difluorophenyl)-5-(thiophen-2-yl)oxazole-4-carboxylic acid (0.078 g, 0.25 mmol) and hydroxybenzotriazole monohydrate (0.039 g, 0.25 mmol) in DMF (2 mL) was added a 0.5M ammonia in dioxane solution (1.5 mL, 0.75 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. 1-(3-(Dimethylamino)propyl)-3-ethyl-carbodiimide hydrochloride (0.054 g, 0.28 mmol) was then added and the resulting mixture stirred at room temperature overnight. The solvent was removed in vacuo and the residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(thiophen-2-yl)oxazole-4-carboxamide (0.0031 g, 0.01 mmol, 4%) as a white solid. 1H NMR (DMSO) 7.25 (1H, dd), 7.40 (2H, t), 7.69-7.76 (3H, m), 7.84 (1H, dd), 8.17 (1H, dd). LCMS (2) Rt: 2.73 min; m/z (ES+) 307.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[P:6]([O-:23])([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1(C)C=CC=CC=1>[P:6]([Cl:4])([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:23]
Reactant: [O-]P(OCc1ccccc1)OCc1ccccc1
Reactant: O=S(=O)(Cl)Cl
Solvent: Cc1ccccc1
Product: O=P(Cl)(OCc1ccccc1)OCc1ccccc1
Reaction time: 1.25 h

Procedure:
A solution of sulphuryl chloride (3.48 g) in toluene (25 ml) was added to a stirred solution of dibenzyl phosphite (6.08 ml) in toluene (75 ml) under nitrogen. The mixture was stirred for 75 min. under nitrogen, washed with 8% sodium bicarbonate solution (75 ml) and the organic layer separated and dried over anhydrous sodium sulphate. After filtration the filtrate was evaporated and dried to give dibenzyl chlorophosphate (7.75 g) as a colourless oil. Potassium carbonate (1.81 g) was added to a solution of 5-hydroxy-1,4-naphthalenedione (2.18 g) in acetonitrile (300 ml) with stirring at room temperature. Freshly prepared dibenzyl chlorophosphate (7.75 g, see above) in acetonitrile (50 ml) was added and the mixture stirred for 20 h. Potassium carbonate (907 mg) was then added and a further quantity (907 mg) of potassium carbonate added after another 24 h. The mixture was evaporated to dryness and dried in vacuo to give an oil. The oil was subjected to column chromatography (silica, 500 g, 70-230 mesh) eluting with dichloromethane:acetone (96:4). Fractions (250 ml) were collected and fractions 4-12 combined and the solvent evaporated. After drying in vacuo the title compound (3.18 g) was obtained as an orange solid; δ(CDCl3) 5.28 (OCH2), 7.38 (Ph).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23.[CH3:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](O)=[O:26].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(Cl)Cl.CN(C)C=O.CO.CCCCCC>[CH3:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25]([NH:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23)=[O:26]
Reactant: Cc1ccccc1C(=O)O
Reactant: Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CCCCCC
Product: Cc1ccccc1C(=O)Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
Yield: 72.5 %

Procedure:
Preparation of example 23 from the title compound of Example 7 (hydrochloride) (22 mg, 0.08 mmol), 2-methyl-benzoic acid (11 mg, 0.08 mmol), triethylamine (0.014 mL, 0.10 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (33 mg, 0.088 mmol) in CH2Cl2 (0.3 mL) and N,N-dimethylformamide (0.3 mL) was carried out analogously to Example 11. Silica gel chromatography (8:5:2 CH2Cl2:hexane:methanol), also in an analogous manner, afforded the title compound (23 mg, 0.058 mmol) as a yellow powder in 73% yield.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)=[CH:8][CH:9]=2)[C:4]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[C:3]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:36][C:37]([O:39][CH3:40])=[O:38]>CC(C)=O>[CH3:40][O:39][C:37](=[O:38])[CH2:36][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:2]([CH3:1])[C:3]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:4]3[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:13]=1
Reactant: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(O)cc3)cc12
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(OCC(=O)OC)cc3)cc12

Procedure:
The desired product was prepared using a procedure similar to step 1 of example 4. Thus, 4-(1-methyl-3-pentyl-2-phenyl-1H-indol-5-yl)-phenol (0.180 g, 0.491 mmol) was reacted with K2CO3 (0.088 g, 0.639 mmol) and methyl bromoacetate (0.098 g, 0.639 mmol) in acetone (5 ml) to give the product (0.184 g, 0.417 mmol, 85%) as a viscous oil. 1H NMR (DMSO-d6) δ 0.76 (t, J=7.2 Hz, 3H), 1.15-1.22 (m, 4H), 1.51-1.56 (m, 2H), 2.65 (t, J=7.3 Hz, 2H), 3.56 (s, 3H), 3.71 (s, 3H), 4.83 (s, 2H), 7.01 (d, J=8.6 Hz, 2H), 7.41-7.45 (m, 3H), 7.47-7.50 (m, 2H), 7.54 (t, J=7.2 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.73 (s, 1H); [ESI(+)], m/z 442 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH2:14][NH:15][C:16]([CH:18]3[O:23][CH2:22][CH2:21][NH:20][CH2:19]3)=[O:17])=[C:11]([CH3:13])[N:12]=2)=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]([C:28]1[CH:29]=[C:30](OB(O)O)[CH:31]=[CH:32][CH:33]=1)=[O:27]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([CH2:14][NH:15][C:16]([CH:18]3[O:23][CH2:22][CH2:21][N:20]([C:32]4[CH:33]=[C:28]([CH:29]=[CH:30][CH:31]=4)[C:26]([O:25][CH3:24])=[O:27])[CH2:19]3)=[O:17])=[C:11]([CH3:13])[N:12]=2)=[CH:6][CH:7]=1
Reactant: COC(=O)c1cccc(OB(O)O)c1
Reactant: Cc1nc(-c2ccc(Cl)cc2)sc1CNC(=O)C1CNCCO1
Product: COC(=O)c1cccc(N2CCOC(C(=O)NCc3sc(-c4ccc(Cl)cc4)nc3C)C2)c1
Yield: 71 %

Procedure:
Using N-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methyl]morpholine-2-carboxamide (29.5 mg, 0.0838 mmol) and 3-(methoxycarbonyl)phenylboric acid (30.2 mg, 0.168 mmol), the same procedure was followed as in Example 2 to give 28.9 mg (71%) of the desired compound as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([OH:12])=[CH:7][CH:8]=2)[N:3]=1.[O:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.COC[C@@H](O)C>O>[CH3:17][O:13][CH2:14][C@H:15]([O:12][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[CH:11][C:2]([CH3:1])=[N:3]2)=[CH:8][CH:7]=1)[CH3:16]
Reactant: Cc1ccc2ccc(O)cc2n1
Reactant: C1CCOC1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: COC[C@H](C)O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Product: COC[C@@H](C)Oc1ccc2ccc(C)nc2c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 73.2 %

Procedure:
To a solution of 2-methylquinolin-7-ol (0.20 g, 1.3 mmol) in tetrahydrofuran (1.1 mL, 1.3 mmol) was added triphenylphosphine (0.82 g, 3.1 mmol), diethyl azodicarboxylate (0.32 mL, 2.0 mmol), and (S)-1-methoxypropan-2-ol (0.16 mL, 1.6 mmol) and the resultant mixture allowed to stir at ambient temperature for 24 hours. The reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (2×20 mL). The combined organic extracts dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography on C18 (0-80% acetonitrile/water) afforded the title compound (0.22 g, 66%).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])([CH3:8])[NH:3]1.[I-].[K+].Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH:23]=[CH2:24]>CN1CCCC1=O>[CH2:24]([N:3]1[C:4]([CH3:9])([CH3:8])[CH2:5][CH2:6][CH2:7][C:2]1([CH3:10])[CH3:1])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=[CH2:14]
Reactant: C=CCCCCCCCCCBr
Reactant: CC1(C)CCCC(C)(C)N1
Agent: [I-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: C=CCCCCCCCCCN1C(C)(C)CCCC1(C)C
Temperature: 120 °C
Yield: 86.4 %

Procedure:
2459 g of N-methylpyrrolidinone and 1013 g 2,2,6,6-tetramethylpiperidine were stirred and heated under inert atmosphere at atmospheric pressure. Granular potassium iodide (527 g) was added gradually over 45 minutes. At a slurry temperature of 112° C., 11-bromo-1-undecene (647 g) was added. The temperature was raised to 120° C. within 15 minutes, maintained at 120-135° C. for three hours and 100-120° C. for four hours. The slurry was cooled to room temperature and partitioned between aqueous NaOH and hexane to give two homogeneous liquid layers. The upper organic layer was separated and distilled below atmospheric pressure to remove a volatile mixture including hexane and tetramethylpiperidine (TMP). The portion remaining after hexane and TMP removal was distilled at 155-164° C./3 mmHg to give 704 g of 1-(10-undecenyl)-2,2,6,6-tetramethylpiperidine (98% purity by GC) as a colorless liquid. The structure was identified by NMR, GC-MS, and High Resolution MS.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]2[O:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:12]=2)[CH:10]=1)[C:5](O)=[O:6].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.[NH2:45][C:46]([CH3:50])([CH3:49])[CH2:47][OH:48]>CN(C)C=O.O>[OH:48][CH2:47][C:46]([NH:45][C:5](=[O:6])[C:4]1[CH:8]=[C:9]([C:11]2[O:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:12]=2)[CH:10]=[C:2]([CH3:1])[CH:3]=1)([CH3:50])[CH3:49]
Reactant: Cc1cc(C(=O)O)cc(-c2cc3nccc(-c4ccccc4)c3o2)c1
Reactant: CC(C)(N)CO
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: CN1CCOCC1
Product: Cc1cc(C(=O)NC(C)(C)CO)cc(-c2cc3nccc(-c4ccccc4)c3o2)c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 41.8 %

Procedure:
3-Methyl-5-(7-phenyl-furo[3,2-b]pyridin-2-yl)-benzoic acid (79 μmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidhydrochlorid (86,592 μmol) are dissolved in N,N-dimethylformamid (300.00 μl) and 4-methylmorpholin (157.354 μmol) and 1-hydroxybenzotriazolhydrat (86.849 μmol) are added and stirred 5 min at RT. A solution of 2-amino-2-methyl-propan-1-ol (80,000 μmol) in N,N-dimethylformamid (100.00 μl) is added. The mixture is stirred 4.5 h at RT. The reaction solution is poured into water and extracted with ethylacetate. The combined organic layers are dried over MgSO4 and the solvent is removed in vacuo. The product is isolated after reversed phase column chromatography as yellow solid (33 μmol, 42% yield). HPLC (method A): Rt 2.55 min (purity 98.5%); LCMS (ESI+) (method E): Rt 2.199 min, M+H+401.1 m/z; 1H NMR (500 MHz, DMSO-d6) δ [ppm] 8.60 (d, J=5.1, 1H), 8.18 (s, 1H), 8.16-8.10 (m, 2H), 7.96 (s, 1H), 7.77 (s, 1H), 7.70 (d, J=8.9, 2H), 7.65 (dd, J=14.7, 6.4, 3H), 7.58 (d, J=7.4, 1H), 4.16 (br, 1H), 3.54 (s, 2H), 2.47 (s, 3H), 1.35 (s, 6H).
Reaction SMILES: P(Cl)(Cl)[Cl:2].C(NC(C)C)(C)C.[CH:12]([N:15]([PH:19][N:20]([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH:16]([CH3:18])[CH3:17])([CH3:14])[CH3:13].C(O)C>C1(C)C=CC=CC=1>[CH:24]([N:20]([P:19]([N:15]([CH:12]([CH3:14])[CH3:13])[CH:16]([CH3:17])[CH3:18])[Cl:2])[CH:21]([CH3:23])[CH3:22])([CH3:26])[CH3:25]
Reactant: CC(C)N(PN(C(C)C)C(C)C)C(C)C
Reactant: ClP(Cl)Cl
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CC(C)NC(C)C
Product: CC(C)N(C(C)C)P(Cl)N(C(C)C)C(C)C

Procedure:
Bis(diisopropylamino)chlorophosphine was synthesized by reacting phosphorous trichloride and diisopropylamine in toluene. Fifty ml of the resulting bis(diisopropylamino)phosphine was placed in a 250 ml flask and 3.01 ml of ethanol added slowly over a two minute period and the reaction allowed to proceed for several days. After filtering the mixture and removing the solvent, the structure of the bis(diisopropylamino)ethylphosphite ester reagent was analyzed by 31P and 1H NMR (31P NMR in CD3CN 125.9 ppm).
Reaction SMILES: C([N:4]1[CH2:10][CH2:9][C:8]2[CH:11]=[C:12]([O:19][CH3:20])[C:13]([S:15](=[O:18])(=[O:17])[NH2:16])=[CH:14][C:7]=2[CH2:6][CH2:5]1)(=O)C.[ClH:21]>>[ClH:21].[CH3:20][O:19][C:12]1[C:13]([S:15](=[O:18])(=[O:17])[NH2:16])=[CH:14][C:7]2[CH2:6][CH2:5][NH:4][CH2:10][CH2:9][C:8]=2[CH:11]=1
Reactant: COc1cc2c(cc1S(N)(=O)=O)CCN(C(C)=O)CC2
Agent: Cl
Product: COc1cc2c(cc1S(N)(=O)=O)CCNCC2

Procedure:
The sulfonamide (2.3 g, 0.007 m) was suspended in 3N hydrochloric acid and heated to reflux for 16 hours. The mixture was concentrated in vacuo and the residue crystallized from methanol to give 8-methoxy-7-sulfamoyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, m.p. 270°-274°.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][OH:9].[C:10]([O-:13])([O-])=[O:11].[K+].[K+]>C(Cl)Cl>[OH:9][N:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])[C:10](=[O:11])[O:13][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1ccccc1NO
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: Cc1ccccc1N(O)C(=O)Oc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol =42%) of the title compound as a colorless solid (mp=98° C.).
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)=[CH2:5].[F-].[Cs+].[CH:15]1([CH:21]=[CH:22][C:23]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[OH:32])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>CS(C)=O>[CH:15]1([CH:21]([CH2:3][C:4]([C:6]2[O:7][CH:8]=[CH:9][CH:10]=2)=[O:5])[CH2:22][C:23]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[OH:32])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: C=C(O[Si](C)(C)C)c1ccco1
Reactant: O=C(C=CC1CCCCC1)c1cc(F)ccc1O
Agent: [Cs+]
Agent: [F-]
Solvent: CS(C)=O
Product: O=C(CC(CC(=O)c1cc(F)ccc1O)C1CCCCC1)c1ccco1
Temperature: 70 °C

Procedure:
1-Trimethylsilyloxy-1-(furan-2-yl)ethylene (1.64 g, 9.0 mmol; prepared according to J. Chem. Soc., Perkin Trans. I 1989, 1585) and CsF (0.41 g, 2.7 mmol) were added to a suspension of 3-cyclohexyl-1-(2-hydroxy-5-fluorophenyl)-2-propen-1-one on Wang resin (3.0 g, 1.8 mmol) in dimethyl sulfoxide (40 mL). The reaction mixture was heated to 70° C. for 3 h and the reaction was quenched with 10% AcOH/CH2Cl2. The resin was filtered, washed with DMF (×2) and alternating MeOH and CH2Cl2 (×5), and dried under high vacuum overnight to give 3.31 g of 3-cyclohexyl-1-(2-hydroxy-5-fluorophenyl)-5-(furan-2-yl)-1,5-pentanedione on Wang resin.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:9]=[C:10]3[C:16]([C:17]4[CH:18]=[N:19][NH:20][CH:21]=4)=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:22]O>C(O)(=O)C>[C:1]1([S:7]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]4[CH:21]=[N:20][NH:19][CH:18]=4)=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[O:22])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OO
Reactant: c1ccc(Sc2cnc3[nH]cc(-c4cn[nH]c4)c3c2)cc1
Solvent: CC(=O)O
Product: O=S(c1ccccc1)c1cnc2[nH]cc(-c3cn[nH]c3)c2c1
Reaction time: 72 h
Yield: 64.9 %

Procedure:
A mixture of sulfide 8 (20 mg, 0.068 mmol) and 30% aqueous H2O2 (10.5 μL, 0.103 mmol) in glacial acetic acid (224 μL) was stirred for 72 h then purified by preparative LCMS (column LUNA 10 μl C18(2) 00G-4253-V0 250×50 mm) using water—acetonitrile (0.1% AcOH) as eluent (in gradient; flow 80 mL/min) to give sulfoxide 9 as a white solid (13.6 mg, 64%); 1H NMR (400 MHz, CDCl3+6 drops CD3OD) δ 7.35-7.50 (m, 4H), 7.60 (m, 2H), 7.78 (s, 2H), 8.35 (d, J=2.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H).