Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=O)[CH:5]=[C:6]([NH2:10])OCC)C.[Cl:12][C:13]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:14]=1[CH2:15][NH:16][NH2:17]>>[NH2:10][C:6]1[NH:17][N:16]([CH2:15][C:14]2[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:13]=2[Cl:12])[C:4](=[O:3])[CH:5]=1
Reactant: CCOC(=O)C=C(N)OCC
Reactant: NNCc1ccc(Cl)cc1Cl
Product: Nc1cc(=O)n(Cc2ccc(Cl)cc2Cl)[nH]1

Procedure:
From 17.5 g of β-amino-β-ethoxyacrylic acid ethyl ester and 20.2 g of 2,4-dichlorobenzylhydrazine analogously to the procedure described in Example 45, 11 g of the compound identified above, as colorless crystals of melting point 189°, corresponding to 40% of theory, are obtained.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[C:20]([NH2:24])([CH3:23])([CH3:22])[CH3:21]>C(Cl)Cl.C1COCC1>[C:20]([NH:24][C:6]([C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)=[O:8])([CH3:23])([CH3:22])[CH3:21]
Reactant: O=C(O)c1ccco1
Reactant: CC(C)(C)N
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1ccco1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a slurry of furan-2-carboxylic acid (10.0 g, 89 mmol) in 100 mL DCM at 0° C. under nitrogen was added DMF (0.069 ml, 0.89 mmol) and oxalyl chloride (9.9 ml, 112 mmol) slowly in small portions over 5 min. The reaction was allowed to warm to ambient temperature. After 3 h, the clear solution was concentrated in vacuo and the resulting oil was dissolved in 75 mL THF and cooled to 0° C. A solution of tert-butylamine (28 ml, 268 mmol) in 25 mL THF was added dropwise over 1 h. The bath was allowed to expire and the slurry was stirred over the weekend. The reaction was concentrated in vacuo and partitioned between 1N NaOH and DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were concentrated in vacuo to give N-tert-butylfuran-2-carboxamide as a white solid. MS m/z=168 [M+H]+. Calc'd for C9H13NO2: 167.2.
Reaction SMILES: [CH2:1]([N:9]1[C:17]2[C:12](=[C:13]([CH3:26])[CH:14]=[C:15]([CH3:25])[C:16]=2[NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]([CH2:27][CH2:28][C:29]([O:31]C)=[O:30])[CH2:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[OH-].[Na+]>CCO.O>[CH2:1]([N:9]1[C:17]2[C:12](=[C:13]([CH3:26])[CH:14]=[C:15]([CH3:25])[C:16]=2[NH:18][C:19](=[O:24])[C:20]([CH3:21])([CH3:22])[CH3:23])[CH:11]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])[CH2:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCN1CC(CCC(=O)OC)c2c(C)cc(C)c(NC(=O)C(C)(C)C)c21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCN1CC(CCC(=O)O)c2c(C)cc(C)c(NC(=O)C(C)(C)C)c21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75.1 %

Procedure:
N-[(1-Octyl-3-(2-methoxycarbonylethyl)-4,6-dimethylindolin-7-yl)]-2,2-dimethylpropanamide (1.1 g) was dissolved in EtOH (10 ml) and a solution of NaOH (494 mg) in water (3 ml) was added, which was followed by stirring at room temperature for 30 min. EtOH was evaporated under reduced pressure and CHCl3 (50 ml) was added. After washing successively with 5% aqueous citric acid and saturated brine, the mixture was dried over anhydrous sodium sulfate. CHCl3 was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: CHCl3 /MeOH=50/1-10/1) to give 800 mg of the title compound.
Reaction SMILES: Br[C:2]1[O:6][C:5]2[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:4]=2[C:3]=1[C:13](=[O:26])[C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=1.[CH3:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>C(#N)C.ClCCl>[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:2]2[O:6][C:5]3[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:4]=3[C:3]=2[C:13](=[O:26])[C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)[CH2:30][CH2:29]1
Reactant: COc1ccc2c(C(=O)c3cc(OC)c(OC)c(OC)c3)c(Br)oc2c1
Reactant: CN1CCNCC1
Solvent: CC#N
Solvent: ClCCl
Product: COc1ccc2c(C(=O)c3cc(OC)c(OC)c(OC)c3)c(N3CCN(C)CC3)oc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 2-bromo-3-(3,4,5-trimethoxybenzoyl)-6-methoxy-benzo[b]furan (20 mg, 0.047 mmol) in a mixture of acetonitrile/dichloromethane; 1:1 (2 mL) was added N-methylpiperazine (50 μL, excess) and the reaction mixture was stirred at room temperature for 1 hour. After this time the solvent was removed by distillation under vacuum and the product was purified by PTLC (eluent=hexane/ethyl acetate; 4:6+1% triethylamine) to give the title compound as a green yellow paste which was crystallized by freeze drying in t-butanol to give a yellow solid; (8 mg, 43%); 1H NMR (300 MHz, CDCl3) δ 7.07 (s, 2H, benzoyl Hs), 6.93 (d, 1H, J=8.60 Hz), 6.84 (d, 1H, J=2.25 Hz), 6.65 (dd, 1H, J=8.64, 2.30 Hz), 3.92 (s, 3H, OMe), 3.83 (s, 6H, 2×OMe), 3.78 (s, 3H, OMe), 3.66-3.64 (bm, 4H), 2.65-2.63 (bm, 4H), 2.40 (s, 3H, N-Me); 13C NMR (75 MHz, CDCl3) δ 188.76 (CO), 162.24, 155.88, 152.72, 149.06, 141.09, 135.36, 121.68, 119.64, 110.42, 106.11, 155.88, 95.63, 60.64, 55.88, 55.44, 53.88, 47.06, 45.29.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N:22]([CH3:29])[CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[C:5]([CH3:21])=[C:6]([CH:20]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:19])[NH:13][C:14]([CH3:18])=[CH:15][C:16]=1[CH3:17])=[O:8].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[C:59](O)(=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([N:22]([CH3:29])[CH:23]2[CH2:28][CH2:27][N:26]([C:59](=[O:64])[C:60]([CH3:63])([CH3:62])[CH3:61])[CH2:25][CH2:24]2)[C:5]([CH3:21])=[C:6]([CH:20]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:19])[NH:13][C:14]([CH3:18])=[CH:15][C:16]=1[CH3:17])=[O:8]
Reactant: CC(C)(C)C(=O)O
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)cc(N(C)C3CCNCC3)c2C)c(=O)[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1cc(C)c(CNC(=O)c2cc(Br)cc(N(C)C3CCN(C(=O)C(C)(C)C)CC3)c2C)c(=O)[nH]1
Reaction time: 18 h
Yield: 49.1 %

Procedure:
To a stirred solution of 5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-3-(methyl(piperidine-4-yl)amino)benzamide (0.05 g, 0.112 mmol) in DMF (2 mL), EDCI.HCl (0.064 g, 0.336 mmol), HOBt (0.03 g, 0.22 mmol), triethyl amine (0.03 g, 0.336 mmol) and pivalic acid (0.023 g, 0.224 mmol) were added at room temperature and stirred at same temperature for 18 h. On completion, water was added and extracted with 10% MeOH/DCM. Combined organic layers were dried, concentrated giving crude material; which then purified by column chromatography to afford the desired compound (0.03 g, 56%). LCMS: 545.20 (M+1)+; HPLC: 98.60% (@ 254 nm) (Rt; 6.355; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate.: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.46 (s, 1H), 8.20 (t, 1H, J=4.4 Hz), 7.25 (d, 1H, J=2.8 Hz), 7.05 (d, 1H, J=1.2 Hz), 5.85 (s, 1H), 4.23-4.25 (m, 4H), 3.00 (m, 1H), 2.76 (t, 2H, J=12.4 Hz), 2.54 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H), 2.10 (s, 3H), 1.62-1.65 (m, 2H), 1.42-1.48 (m, 2H), 1.18 (s, 9H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5](S(OCCC=CC=C)(=O)=O)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH2:25]([NH2:32])[C:26]1C=[CH:30][CH:29]=[CH:28][CH:27]=1.[OH-].[Na+]>C(#N)C>[CH2:1]([NH:32][CH2:25][CH2:26][CH:27]=[CH:28][CH:29]=[CH2:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NCc1ccccc1
Reactant: C=CC=CCCOS(=O)(=O)c1ccc(C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C=CC=CCCNCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 44.5 %

Procedure:
A solution of hexa-3,5-dien-1-yl 4-methylbenzenesulfonate (1.90 g, 7.53 mmol) and triethylamine (1.39 mL, 10.0 mmol) in acetonitrile (70 mL) was treated with benzylamine (2.45 mL, 22.5 mmol), and the mixture was stirred at room temperature for 16 hours. The solution was then heated to reflux for 3 hours, cooled, and treated with 1.0 N aqueous sodium hydroxide. The mixture was extracted three times with ethyl acetate. (A portion of the extracts were lost due to spillage). The combined organic phases were dried over magnesium sulfate and concentrated to provide a pale yellow oil. The yellow oil was purified by radial thin-layer chromatography, eluting with 25% ethyl acetate/hexane, to provide a colorless oil (628 mg, 45%). 1H NMR (300 MHz, CDCl3) δ7.32 (m, 4H), 7.26 (m, 1H), 6.32 (td, J=17, 10 Hz, 1H), 6.12 (dd, J=15, 10 Hz, 1H), 5.68 (td, J=15, 7 Hz, 1H), 5.12 (d, J=17 Hz, 1H), 5.00 (d, J=10 Hz, 1H), 3.80 (s, 2H), 2.71 (t, J=7 Hz, 2H), 2.32 (q, J=7 Hz, 2H), 1.52 (broad s, 1H). Mass spec (ES+) m/z 188.4 (M+H+, 100%).
Reaction SMILES: [F:1][CH:2]([F:12])[C:3]1[N:4]([CH3:11])[CH:5]=[C:6]([OH:10])[C:7](=[O:9])[CH:8]=1.[C:13]([CH:17](OC)[OH:18])([F:16])([F:15])[F:14].C(=O)([O-])[O-].[K+].[K+]>>[F:12][CH:2]([F:1])[C:3]1[N:4]([CH3:11])[C:5]([CH:17]([OH:18])[C:13]([F:16])([F:15])[F:14])=[C:6]([OH:10])[C:7](=[O:9])[CH:8]=1
Reactant: Cn1cc(O)c(=O)cc1C(F)F
Reactant: COC(O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cn1c(C(F)F)cc(=O)c(O)c1C(O)C(F)(F)F
Temperature: 100 °C
Yield: 4.5 %

Procedure:
A suspension of 2-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one (0.50 g, 2.85 mmol), CF3CH(OH)OCH3 (2.37 g, 18.2 mmol) and potassium carbonate (0.122 g, 0.88 mmol) in a sealed parallel reactor test tube was heated to about 100° C. The progress of the reaction was monitored by HPLC Method 1 (Example 24), and only one major product peak was detected (HPLC peak percent area was about 20% after 1.5 h, and 38% after 3 h). The reaction mixture was heated for another 21 h, then cooled down to RT, and some white solid separated. The solid was collected by suction filtration. HPLC analysis of the solid dissolved in methanol showed the presence of 2-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one and 6-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one in 18/82 ratio. A portion of the solid was purified by column chromatography on silica gel (conc. NH4OH/isopropanol 10/100 v/v as eluant) to afford 6-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (35 mg). HPLC Method 1 (Example 24), RT=11.3 min, HPLC purity (peak percent area): 97.9% at λ=280 nm. 1H NMR (DMSO-d6+1 drop of D2O) δ ppm: 7.12 (t, J=52.8 Hz, 1H), 6.56 (s, 1H), 5.83 (b, 1H), 3.79 (s, 3H). 19F NMR (DMSO-d6+1 drop of D2O) δ ppm: −73.3 (3F), −117.8 (2F). MS-ESI (m/z) 274.1 [M+1]+, 256.1, 228.1, 208.1 (100%), 180.1.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:40])[CH2:9][CH2:10][CH:11]1[CH2:17][C:16]2[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=[CH:21][C:15]=2[C:14]2=[C:24]([CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)[C:25]3[CH:26]=[CH:27][C:28]([C:31](O)=[O:32])=[CH:29][C:30]=3[N:13]2[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:41][O:42][CH:43]([O:51][CH3:52])[CH2:44][N:45]([CH3:50])[S:46]([NH2:49])(=[O:48])=[O:47].C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH:34]1([C:24]2[C:25]3[CH:26]=[CH:27][C:28]([C:31]([NH:49][S:46]([N:45]([CH2:44][CH:43]([O:42][CH3:41])[O:51][CH3:52])[CH3:50])(=[O:48])=[O:47])=[O:32])=[CH:29][C:30]=3[N:13]3[CH2:12][CH:11]([CH2:10][CH2:9][N:8]([CH3:40])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:17][C:16]4[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=[CH:21][C:15]=4[C:14]=23)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: COC(CN(C)S(N)(=O)=O)OC
Reactant: COc1ccc2c(c1)CC(CCN(C)C(=O)OC(C)(C)C)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)O)cc21
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: ClCCCl
Product: COc1ccc2c(c1)CC(CCN(C)C(=O)OC(C)(C)C)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)NS(=O)(=O)N(C)CC(OC)OC)cc21
Temperature: 40 °C
Reaction time: 3 h

Procedure:
To a solution of 6-{2-[(tert-butoxycarbonyl)(methyl)amino]ethyl}-13-cyclohexyl-3-methoxy-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid in DCM (0.07M), N-(2,2-dimethoxyethyl)-N-methylsulfamide (2 eq, Example 1, Step 1), EDC (3 eq) and DMAP (5 eq) were added. The mixture was stirred at 40° C. for 3 h, then diluted with EtOAc and washed with 1N HCl, 1N NaOH solution and brine. The organic phase was dried over Na2SO4 and evaporated in vacuo and the residual material was used in the next step without purification. (ES+) m/z 727 (M+H)+.
Reaction SMILES: CC1(C)[O:6][C@@H:5]([C:7](O)=[O:8])[CH2:4][O:3]1.C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.Cl.[N:47]1([C:53]2[CH:58]=[CH:57][C:56]([N:59]3[CH2:63][C@H:62]([CH2:64][O:65][C:66]4[CH:70]=[CH:69][O:68][N:67]=4)[O:61][C:60]3=[O:71])=[CH:55][C:54]=2[F:72])[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>ClCCl>[OH:6][C@H:5]([CH2:7][OH:8])[C:4]([N:50]1[CH2:49][CH2:48][N:47]([C:53]2[CH:58]=[CH:57][C:56]([N:59]3[CH2:63][C@H:62]([CH2:64][O:65][C:66]4[CH:70]=[CH:69][O:68][N:67]=4)[O:61][C:60]3=[O:71])=[CH:55][C:54]=2[F:72])[CH2:52][CH2:51]1)=[O:3]
Reactant: O=C1O[C@@H](COc2ccon2)CN1c1ccc(N2CCNCC2)c(F)c1
Reactant: CC1(C)OC[C@H](C(=O)O)O1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C([C@H](O)CO)N1CCN(c2ccc(N3C[C@H](COc4ccon4)OC3=O)cc2F)CC1
Yield: 19.8 %

Procedure:
A solution of 2,2-dimethyl-1,3-dioxolane-4(R)-carboxylic acid (162 mg, 1.1 mmol) in dichloromethane (20 ml) under nitrogen was cooled with stirring to 4°, and treated successively with dicyclohexylcarbodiimide (227 mg, 1.1 mmol) and 1-hydroxybenzotriazole (147 mg, 1.1 mmol), then stirred at the same temperature for 1 hour. N,N-Diisopropylethylamine (129 mg, 1 mmol) was added, followed by 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (399 mg, 0.92 mmol). The mixture was stirred for 2 hours, allowing the temperature to rise to ambient. Solid was filtered off, and the organic solution washed with water (2×20 ml), dried over magnesium sulfate and evaporated to dryness. The residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 10% MeOH in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (82 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4](F)[CH:3]=1.[C:12](=[O:15])([O-])[O-].[Cs+].[Cs+].[C:18]1([C:24]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN1C(=O)CCC1.O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:29]2[CH2:28][CH2:27][N:26]([C:24]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:25])[CH2:31][CH2:30]2)=[CH:3][C:4]=1[O:15][C:12]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(Br)cc1F
Reactant: O=C(c1ccccc1)N1CCNCC1
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(c1ccccc1)N1CCN(c2ccc([N+](=O)[O-])c(Oc3ccccc3)c2)CC1
Temperature: 110 °C
Yield: 130.9 %

Procedure:
A solution of 4-bromo-2-fluoro-1-nitrobenzene (0.6 g, 2.75 mmol) phenol (0.28 g, 3.02 mmol) and cesium carbonate (1.8 g, 5.5 mmol) in NMP (6 mL) was heated at 70° C. for 12 h, cooled then diluted with H2O (15 mL) and extracted with ethyl acetate (3×10 mL). The organics were washed with brine (8 mL), dried (Na2SO4) then filtered and concentrated in vacuo. The colorless solid was dissolved in NMP (2 mL) to which was added phenyl(piperazin-1-yl)methanone (1.0 g, 5.5 mmol) and the solution was heated to 110° C. for 16 h. The mixture was cooled and then diluted with H2O (15 mL) and extracted with ethyl acetate (3×10 mL). The organics were washed with brine (8 mL), dried (Na2SO4) then filtered and concentrated in vacuo. The residue was subjected to silica gel column chromatography (20% ethyl acetate/hexane) to furnish (4-(4-nitro-3-phenoxyphenyl)piperazin-1-yl)(phenyl)methanone (0.72 g, 1.8 mmol) as a yellow gum, 65% yield. 1H NMR (500 MHz, CDCl3) d (ppm) 8.11 (d, J=9.5 Hz, 1H), 7.51-7.47 (m, 5H), 7.39 (t, J=8.0 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.05 (m, 2H), 6.64 (dd, J=2.5 Hz, 9.5 Hz, 1H), 6.35 (d, J=2.5 Hz, 1H), 4.1-3.1 (m, 8H).+ESI HRMS (calcd for C23H21N3NaO4, M+Na) 426.1430, found 426.1424
Reaction SMILES: [F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14](Cl)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[NH2:18][C:19]1[N:24]=[C:23]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:27][CH:26]=2)[C:22]([CH3:38])=[CH:21][N:20]=1>N1C=CC=CC=1>[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:18][C:19]4[N:24]=[C:23]([C:25]5[CH:26]=[CH:27][C:28]([C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])=[CH:36][CH:37]=5)[C:22]([CH3:38])=[CH:21][N:20]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1
Reactant: O=C(Cl)C1(c2ccc3c(c2)OC(F)(F)O3)CC1
Reactant: Cc1cnc(N)nc1-c1ccc(C(=O)OC(C)(C)C)cc1
Solvent: c1ccncc1
Product: Cc1cnc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1-c1ccc(C(=O)OC(C)(C)C)cc1
Temperature: 90 °C

Procedure:
To 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (91 mg, 0.35 mmol) and tert-butyl 4-(2-amino-5-methylpyrimidin-4-yl)benzoate (50 mg, 0.175 mmol), pyridine (2 mL) was added. The reaction was heated at 90° C. for twenty four hours. The pyridine was evaporated under reduced pressure. The resulting mixture was dissolved in EtOAc and filtered. The filtrate was washed with saturated aqueous NaHCO3 (×3). The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to yield tert-butyl 4-(2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-5-methylpyrimidin-4-yl)benzoate. ESI-MS m/z calc. 509.2, found 510.5 (M+1)+. Retention time 2.18 minutes.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[F:13][C:14]([F:64])([F:63])[C:15]([O:24][CH2:25][C:26]([CH2:48][O:49][C:50]([C:59]([F:62])([F:61])[F:60])([C:55]([F:58])([F:57])[F:56])[C:51]([F:54])([F:53])[F:52])([CH2:33][O:34][C:35]([C:44]([F:47])([F:46])[F:45])([C:40]([F:43])([F:42])[F:41])[C:36]([F:39])([F:38])[F:37])[CH2:27][O:28][CH2:29][CH2:30][CH2:31][OH:32])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17].C(Cl)Cl>C1COCC1>[CH3:8][S:9]([O:32][CH2:31][CH2:30][CH2:29][O:28][CH2:27][C:26]([CH2:33][O:34][C:35]([C:36]([F:39])([F:38])[F:37])([C:40]([F:41])([F:42])[F:43])[C:44]([F:47])([F:46])[F:45])([CH2:48][O:49][C:50]([C:51]([F:52])([F:53])[F:54])([C:55]([F:56])([F:57])[F:58])[C:59]([F:60])([F:61])[F:62])[CH2:25][O:24][C:15]([C:16]([F:19])([F:18])[F:17])([C:20]([F:23])([F:22])[F:21])[C:14]([F:63])([F:64])[F:13])(=[O:11])=[O:10]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCOCC(COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F)(COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F)COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CS(=O)(=O)OCCCOCC(COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F)(COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F)COC(C(F)(F)F)(C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 94.5 %

Procedure:
Triethylamine (Et3N, 9.6 mL) and methanesulfonyl chloride (5.4 mL, 68.4 mmol) were added to a solution of compound 5 (20.2 g, 23.8 mmol) dissolved in THF (100 mL) and anhydrous CH2Cl2 (200 mL) mixed solvent at 0° C. The reaction mixture was then stirred at room temperature overnight. The reaction was quenched with water and extracted with CH2Cl2. Evaporation through rotary evaporation followed by flash chromatography on silica gel using hexane/EtOAc as the eluent afforded product mesylate 6 (20.8 g, 22.5 mmol, 95% yield) as a colorless oil: 1H NMR (500 MHz, CD3COCD3) δ 4.21 (t, J=7.5 Hz, 2H), 4.11 (s, 6H), 3.48 (t, J=5.0 Hz, 2H), 3.42 (s, 2H), 2.94 (s, 3H), 1.94-1.90 (m, 2H); 13C NMR (126 MHz, CD3COCD3) δ 122.9 (q, J=293.0 Hz), 81.2-81.0 (m), 68.6, 68.5, 67.1, 67.0, 47.7, 37.6, 30.7; 19F NMR (470 MHz, CD3COCD3) δ −71.19 (s); MS (APCI) m/z 927 (M+H)+, 831 (M−OMs)+; HRMS (ESI) calcd for C21H18F27O7S, 927.0342 (M+H)+, 944.0608 [M+NH4]+. found 927.0357, 944.0553, respectively.
Reaction SMILES: C1C(I)=C(O)C(I)=C2OC3C([C:17]4(O[C:28](=O)[C:19]5[C:20](Cl)=[C:21](Cl)[C:22](Cl)=[C:23](Cl)[C:18]4=5)C=12)=CC(I)=C(O)C=3I.CN([C:37]1[CH:38]=[CH:39][C:40]2N=C3C(=CC(C=C3)=[N+](C)C)S[C:41]=2[CH:42]=1)C>>[CH:20]1[C:19]2[C:18](=[CH:17][C:37]3[C:38]([CH:28]=2)=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:23]=[CH:22][CH:21]=1
Reactant: O=C1OC2(c3cc(I)c(O)c(I)c3Oc3c2cc(I)c(O)c3I)c2c(Cl)c(Cl)c(Cl)c(Cl)c21
Reactant: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1
Product: c1ccc2cc3ccccc3cc2c1

Procedure:
(8.3 mmol) and 500 mg. of photosensitizing resin were mixed in 100 ml. of chloroform and irradiated. After 148 cc. (6.6 mmol) of oxygen was absorbed the resin was filtered off, the solution was decolorised with charcoal and evaporated to dryness. The residue was fractionally recrystallized from chloroform to yield anthracene endoperoxide, mp 137°-143°. Rose bengal attached to IRA-400 and methylene blue attached to IRC-200 both gave the same results.
Reaction SMILES: C[Si](C)(C)N[Si](C)(C)C.[Li].[CH3:11][Si:12]([C:15]#[CH:16])([CH3:14])[CH3:13].[CH:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(OCC)C>O1CCCC1.O>[CH3:11][Si:12]([C:15]#[C:16][CH:17]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:24])([CH3:14])[CH3:13]
Reactant: C#C[Si](C)(C)C
Reactant: O=Cc1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: [Li]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOCC
Product: C[Si](C)(C)C#CC(O)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 100.1 %

Procedure:
Place lithium hexamethyldisilazane (20 mL of a 1M solution in tetrahydrofuran, 20 mmol) under an argon atmosphere and cool to 0° C. Add, by dropwise addition, trimethylsilylacetylene (2.83 mL, 20 mmol) and stir for 1 hour at 0° C. Add benzaldehyde (2.03 mL, 20 mmol) in tetrahydrofuran (10 mL). Allow to warm to room temperature and stir for 1 hour. Pour the mixture into ethyl ether and water, separate the organic phase and evaporate the solvent in vacuo. Filter the oil through silica gel (20% ethyl acetate/hexane) and evaporate the solvent in vacuo to yield 4.09 g of the title compound.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][P:7]([OH:10])([OH:9])=[O:8])[C:2]([OH:4])=[O:3].[NH3:11]>O>[CH2:1]([NH:5][CH2:6][PH2:7])[C:2]([O-:4])=[O:3].[NH4+:11].[CH2:1]([NH:5][CH2:6][P:7]([OH:10])([OH:9])=[O:8])[C:2]([OH:4])=[O:3]
Reactant: N
Agent: O=C(O)CNCP(=O)(O)O
Solvent: O
Product: O=C([O-])CNCP
Product: [NH4+]

Procedure:
In a stirred 10 liter round-bottom flask equipped with a water cooled condenser, thermometer, nitrogen blanket and equilibrating dropping funnel, was charged 500 grams of Solution 1 and 968 grams of water. With stirring, 2409 grams of glyphosate acid in the form of wet cake were added. Then 1623 grams of 25% aqueous ammonia were added at such a rate that the temperature of reaction mixture did not exceed 85° C. The pH of the reaction mixture was measured, and up to 85 grams of 25% aqueous ammonia were added in increments until a pH of 6.3-6.7 was obtained. The assay was determined by high pressure liquid chromatography by standard methods and sufficient additional water added to give an ammonium glyphosate solution with a glyphosate assay of 41.7% a.e. or 525 g a.e./l.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14](=O)[NH:13][CH:12]=2)[CH:6]=[CH:5][N:4]=1.P(Cl)(Cl)([Cl:24])=O.Cl.O.N>O1CCOCC1.CCOC(C)=O>[Cl:24][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([CH2:10][CH2:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=2)=[CH:12][N:13]=1
Reactant: COc1cc(CCc2c[nH]c(=O)c3ccccc23)ccn1
Reactant: O=P(Cl)(Cl)Cl
Agent: Cl
Agent: N
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COc1cc(CCc2cnc(Cl)c3ccccc23)ccn1
Temperature: 65 °C
Reaction time: 7 h

Procedure:
Under a N2 atmosphere, 160 mg (0.57 mmol) of 4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-2H-isoquinolin-1-one in 3.7 ml of acetontrile are mixed with 131 μl (1.43 mmol) of phosphorus oxychloride and 0.28 ml of 4 N HCl In dioxane and stirred for 7 h at 65° C. After cooling to RT, water/NH3 conc. 10:1 and EtOAc are added, the water phase is separated and extraction effected twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation to form 1-chloro-4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline; 1H NMR (DMSO-d6) δ 8.30 (d, 1H), 8.27 (d, 1H), 8.13 (s, 1H), 8.03 (d, 1H), 7.94 (t, 1H), 7.85 (t, 1H), 6.90 (d, 1H), 6.73 (s, 1H), 3.80 (s, H3C), 3.32 (t, H2C), 2.95 (t, H2C).