Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl[C:12]([F:17])([F:16])C([O-])=O.[Na+].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[F:16][CH:12]([F:17])[O:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([C:8]#[N:9])=[N:6][CH:7]=1
Reactant: O=C([O-])C(F)(F)Cl
Reactant: Cc1cc(O)cnc1C#N
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(OC(F)F)cnc1C#N

Procedure:
A solution of 5-hydroxy-3-methyl-pyridine-2-carbonitrile (CAS registry 228867-86-5) (228 mg, 1.70 mmol), sodium chlorodifluoroacetate (CAS registry 1895-39-2) (518 mg, 3.40 mmol) and K2CO3 (705 mg, 5.10 mmol) in DMF (7 ml) was stirred for 0.5 h at 100° C. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl soln. and brine. The aqueous layers were reextracted with EtOAc, the combined organic layers dried over Na2SO4, filtrated and the filtrate was concentrated. The title compound was obtained as a colourless oil after flash chromatography on silica gel (cyclohexane/EtOAc gradient 0-3 min 95:5, 3-35 min 95:5 to 60:40).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])(C)C.Cl.C([O-])([O-])=O.[Na+].[Na+].C(=O)(ON1C(=O)CCC1=O)OCC1[C:44]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:38]2[C:33]1=[CH:34][CH:35]=[CH:36][CH:37]=2>O1CCOCC1.CCOC(C)=O>[CH:41]1[C:40]2[CH:4]([CH2:1][O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=3)[C:10]([OH:12])=[O:11])=[O:7])[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:39]=2[CH:44]=[CH:43][CH:42]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(F)c(Cl)c1)C(=O)O
Reactant: O=C(OCC1c2ccccc2-c2ccccc21)ON1C(=O)CCC1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: O=C(N[C@@H](Cc1ccc(F)c(Cl)c1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
The (S)-2-((tert-butoxycarbonyl)amino)-3-(3-chloro-4-fluorophenyl)propanoic acid (183.0 mg, 0.576 mmol) was suspended in a 4M hydrochloric acid (1440 μl, 5.76 mmol) solution in dioxane at room temperature for 2 h. After solvent evaporation, the crude product was cooled to 0° C. using an ice bath before being dissolved in MeCN (288 μl) and a 2.0M aqueous solution of Na2CO3 (288 μl, 0.576 mmol). (9H-fluoren-9-yl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate (194 mg, 0.576 mmol) was added to the solution and the reaction mixture was allowed to stir for 30 min. The mixture was diluted in 5.0 mL of EtOAc and the aqueous phase was neutralized with a few drops of an aqueous 1N HCl solution. The organic solvents were evaporated and the crude product was then partitioned between a saturated aqueous NH4Cl solution and EtOAc. The crude product was extracted with EtOAc. The organic fractions were combined and dried over anhydrous sodium sulfate. After filtration and concentration, a yellow crystalline solid was obtained. Purification by silica gel chromatography using 100% hexanes to 30% EtOAc/Hexanes yielded the desired product as a white crystalline solid. A second purification on silica gel was performed using 100% DCM to 20% MeOH/DCM as eluant. The desired product, (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-chloro-4-fluorophenyl)propanoic acid, was obtained as a white solid (0.111 g, 44%). 1H NMR (400 MHz, methanol-d4) δ 7.79 (d, J=7.5 Hz, 2H), 7.60 (t, J=6.8 Hz, 2H), 7.47-7.23 (m, 5H), 7.25-7.14 (m, 1H), 7.13 (d, J=9.0 Hz, 1H), 4.52-4.11 (m, 4H), 3.19 (dd, J=14.3, 4.6 Hz, 1H), 2.92 (dd, J=13.9, 9.7 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C@@H:14]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]4[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=4[CH:31]=3)[CH2:13][N:12]([S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[C@H:11]([CH2:42][C:43]([CH3:48])([CH3:47])[C:44](O)=[O:45])[CH2:10]2)=[CH:5][CH:4]=1.[CH3:49][O:50][CH2:51][CH2:52][NH2:53]>>[CH3:49][O:50][CH2:51][CH2:52][NH:53][C:44](=[O:45])[C:43]([CH3:47])([CH3:48])[CH2:42][C@@H:11]1[CH2:10][C@H:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C@@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]3[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=3[CH:31]=2)[CH2:13][N:12]1[S:32]([C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=1)(=[O:33])=[O:34]
Reactant: COCCN
Reactant: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@H](CC(C)(C)C(=O)O)C[C@@H]3c3ccc(OC)cc3)cc21
Product: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@H](CC(C)(C)C(=O)NCCOC)C[C@@H]3c3ccc(OC)cc3)cc21

Procedure:
According to general procedure D, 150 mg of 3-[(2S,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-1-(toluene-4-sulfonyl)-piperidin-2-yl]-2,2-dimethyl-propionic acid (from example 65b) and 2-methoxyethylamine are used to afford the title compound as a brown oil. Rf=0.18 (EtOAc-heptane 5:1); Rt=5.05.
Reaction SMILES: [O:1]1[C@@:5]2([CH:10]3[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]3)[CH2:6]2)[CH2:4][NH:3][C:2]1=[O:13].Br[C:15]1[O:16][C:17]([Si:21]([CH3:24])([CH3:23])[CH3:22])=[C:18]([Br:20])[CH:19]=1>>[Br:20][C:18]1[CH:19]=[C:15]([N:3]2[CH2:4][C@:5]3([CH:10]4[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]4)[CH2:6]3)[O:1][C:2]2=[O:13])[O:16][C:17]=1[Si:21]([CH3:24])([CH3:23])[CH3:22]
Reactant: O=C1NC[C@@]2(CN3CCC2CC3)O1
Reactant: C[Si](C)(C)c1oc(Br)cc1Br
Product: C[Si](C)(C)c1oc(N2C[C@@]3(CN4CCC3CC4)OC2=O)cc1Br

Procedure:
The title compound was prepared by a method analogous to that described in Preparation 3 from (S)-spiro[1-azabicyclo[2.2.2]octan-3,5′-oxazolidin]-2′-one and 2,4-dibromo-5-(trimethylsilyl)furan. The title compound (577 mg) was obtained as a pale yellow solid, m/z 399, 401 (MH+).
Reaction SMILES: CC1(C)CO[CH:5]([CH:8]([C@@H:10]2[C@:27]3([CH3:28])[C@H:13]([C:14]4[C@H:24]([CH2:25][CH2:26]3)[C@:22]3([CH3:23])[C:17]([CH2:18][C@@H:19]([O:37][C:38](=[O:42])[N:39]([CH3:41])[CH3:40])[CH2:20][C@@H:21]3[O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])=[CH:16][CH:15]=4)[CH2:12][CH2:11]2)[CH3:9])[O:4]C1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[Si:30]([O:29][C@@H:21]1[C@@:22]2([CH3:23])[C:17](=[CH:16][CH:15]=[C:14]3[C@@H:24]2[CH2:25][CH2:26][C@@:27]2([CH3:28])[C@H:13]3[CH2:12][CH2:11][C@@H:10]2[CH:8]([CH:5]=[O:4])[CH3:9])[CH2:18][C@@H:19]([O:37][C:38](=[O:42])[N:39]([CH3:41])[CH3:40])[CH2:20]1)([C:33]([CH3:36])([CH3:34])[CH3:35])([CH3:32])[CH3:31]
Reactant: CC(C1OCC(C)(C)CO1)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](OC(=O)N(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)=O
Product: CC(C=O)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](OC(=O)N(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Yield: 66.6 %

Procedure:
In 10 ml of acetone was dissolved 110 mg of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1α-(tert-butyldimethylsilyl)oxy-3β-(N,N-dimethylcarbamoyl)oxypregna-5,7diene, followed by addition of 10 mg of p-toluenesulfonic acid. The mixture was refluxed in an atmosphere of argon gas for 4 hours. The reaction mixture was then worked up in the same manner as Example 156 to give 63 mg of 1α-(tert-butyldimethylsilyl)oxy-3β-(N,N-dimethylcarbamoyl)oxypregna-5,7-diene-20-carbaldehyde showing the following physical properties.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:20]4[S:21][CH:22]=[C:23]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:24]=4)=[O:19])[CH:16]=3)[NH:11][C:10](=[O:31])[C:9]=2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH:18]([OH:19])[C:20]4[S:21][CH:22]=[C:23]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:24]=4)[CH:16]=3)[NH:11][C:10](=[O:31])[C:9]=2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(-c2cccc(Cl)c2)c2cc(C(=O)c3nc(-c4ccccc4)cs3)ccc2[nH]c1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CCOC(=O)c1c(-c2cccc(Cl)c2)c2cc(C(O)c3nc(-c4ccccc4)cs3)ccc2[nH]c1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 81.7 %

Procedure:
A mixture of intermediate (18) (0.0336 mol) in methanol (100 ml) and THF (100 ml) was cooled on an ice bath. Sodium tetrahydroborate (0.0336 mol) was added portionwise. The mixture was stirred at a low temperature for 30 min, then poured out into ice water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue was crystallized from 2-propanone/DIPE. The precipitate was filtered off and dried, yielding 14.2 g (81.6%) of ethyl 4-(3-chlorophenyl)-1,2-dihydro-6-[hydroxy(4-phenyl-2-thiazolyl)methyl]-2-oxo-3-quinolinecarboxylate (intermediate 19), mp. 127° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[O:6][C:5](=[CH:7][C:8](Cl)=[O:9])[C:4](=[O:11])[O:3]1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:29]=[CH:30][C:31]=1[Cl:32])[CH2:17][NH:18][O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[Cl:13][C:14]1[CH:15]=[C:16]([CH:29]=[CH:30][C:31]=1[Cl:32])[CH2:17][N:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)[C:8](=[O:9])[CH:7]=[C:5]1[C:4](=[O:11])[O:3][C:2]([CH3:12])([CH3:1])[O:6]1
Reactant: Clc1ccc(CNOCCCN2CCOCC2)cc1Cl
Reactant: CC1(C)OC(=O)C(=CC(=O)Cl)O1
Product: CC1(C)OC(=O)C(=CC(=O)N(Cc2ccc(Cl)c(Cl)c2)OCCCN2CCOCC2)O1
Yield: 64.7 %

Procedure:
Reaction of (2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl chloride (0.49 mmol) with N-(3,4-dichlorobenzyl)-O-(3-morpholin-4-yl-propyl)-hydroxylamine (0.150 g, 0.49 mmol) as described in the preparation of compound 44-C gave 0.150 g (65% yield) of the title amide as white crystals after chromatography on silica gel: mp 77–78° C. (ether-hexane). 1HNMR 400 MHz (C6D6) δ (ppm): 1.09 (6H, s, CH3), 1.47 (2H, m, CH2), 2.17 (2H, t, J=6.5 Hz, NCH2), 2.22 (4H, m, NCH2), 3.66 (2H, t, J=6.0 Hz, OCH2), 3.73 (4H, m, OCH2), 4.56 (2H, s, NCH2), 6.82 (1H, s, CH), 6.98 (1H, dd, J=2.0 Hz and J=8.0 Hz, aromatic), 7.06 (1H, d, J=8.0 Hz, aromatic), 7.40 (1H, d, J=2.0 Hz, aromatic). Anal. Calcd for C21H26Cl2N2O6: C, 53.28; H, 5.53; N, 5.91. Found: C, 53.31; H, 5.67; N, 5.77.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:37])[C:5]([CH3:36])=[C:6]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:32]C(=O)C)=[C:17]([CH:31]=2)[C:18]([NH:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:22]=2[O:29][CH3:30])=[O:19])[C:7](=[O:11])[C:8]=1[O:9][CH3:10].C(=O)([O-])O.[Na+]>CO.O>[CH3:1][O:2][C:3]1[C:4](=[O:37])[C:5]([CH3:36])=[C:6]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([OH:32])=[C:17]([CH:31]=2)[C:18]([NH:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:22]=2[O:29][CH3:30])=[O:19])[C:7](=[O:11])[C:8]=1[O:9][CH3:10]
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)Nc3cc(OC)ccc3OC)c2)=C(C)C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COC1=C(OC)C(=O)C(Cc2ccc(O)c(C(=O)Nc3cc(OC)ccc3OC)c2)=C(C)C1=O
Yield: 70.1 %

Procedure:
N-[5-(5,6-Dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoyl]-2,5-dimethoxyaniline (0.075 g, 0.147 mmol) was dissolved in methanol (3 ml) and after adding thereto an aqueous saturated sodium hydrogencarbonate solution (3 ml), the solution was stirred at room temperature for 3 hours. After the completion of reaction, the reaction solution was diluted with water and then extracted with ethyl acetate. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was recrystallized from a mixed solvent of ether and hexane (1:1) to obtain the titled compound (0.048 g, 0.103 mmol, 70%).
Reaction SMILES: I[C:2]1[CH:3]=[N:4][O:5][C:6]=1[CH3:7].[CH3:8][O:9][C:10]1[N:15]=[C:14]([CH3:16])[C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)(O)[O-].[Na+].O>COCCOC>[CH3:16][C:14]1[C:13]([C:2]2[CH:3]=[N:4][O:5][C:6]=2[CH3:7])=[CH:12][CH:11]=[C:10]([O:9][CH3:8])[N:15]=1
Reactant: COc1ccc(B(O)O)c(C)n1
Reactant: Cc1oncc1I
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COc1ccc(-c2cnoc2C)c(C)n1
Temperature: 25 °C
Yield: 40.2 %

Procedure:
A mixture of 4-iodo-5-methylisoxazole (18.2 g, 87 mmol), 6-methoxy-2-methylpyridine-3-boronic acid (14.6 g, 87 mmol), sodium bicarbonate (22.0 g, 262 mmol), water (150 mL) and DME (150 mL) was degassed three times with stirring by the application of a vacuum and then introduction of a nitrogen atmosphere. [1,1-Bis(diphenylphosphino)ferrocene]-dichloropalladium (II) (2.14 g, 2.6 mmol) was added in one portion. The reaction mixture was degassed as before. The reaction mixture was then stirred at 80° C. for 4 h, then it was cooled to ambient temperature. Three extractions with EtOAc, drying the combined organic layers over MgSO4, filtration and removal of solvent in vacuo afforded an oil. Flash chromatography (EtOAc:hexane::1:9) and removal of solvent in vacuo from the desired fractions gave the product (7.15 g): 1H-NMR(CDCl3, 300 MHz): δ 8.16 (s, 1H), 7.33 (d, 1H, J=8), 6.63 (d, 1H, J=8), 3.95 (s, 3H), 2.35 (s, 6H); APCI+-MS: 205 (M++H).
Reaction SMILES: [NH2:1][C:2]1[NH:7][C:6](=S)[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][C:11]1([CH2:16][CH3:17])[O:15][CH2:14][CH2:13][O:12]1.[OH-].[NH4+]>[Ni].O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([OH:9])[C:3]=1[CH2:10][C:11]1([CH2:16][CH3:17])[O:15][CH2:14][CH2:13][O:12]1
Reactant: CCC1(Cc2c(N)[nH]c(=S)[nH]c2=O)OCCO1
Agent: [Ni]
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: CCC1(Cc2c(N)ncnc2O)OCCO1

Procedure:
A mixture of 7.72 g (30 mmol) of 6-amino-5-(2-ethyl-1,3-dioxolan-2-ylmethyl)-2-thiouracil, 22.5 g of Raney Ni, 330 mL of water, and 23 mL of concentrated ammonium hydroxide was heated to reflux for 150 minutes. The mixture was filtered warm and then concentrated under vacuum to 6.34 g of tan solid. The solid was slurried in 100 mL of ethyl ether and solids collected by filtration. The solids were dried to 6.16 g (91.2%) of 6-amino-5-(2-ethyl-1,3-dioxolan-2-ylmethyl)-4-pyrimidinol as an off white solid. nmr (500 MHz, dmso-d6) δ0.82 (t, J=7.4 Hz, 3H), 1.54 (q, J=7.4 Hz, 2H), 2.63 (s, 2H), 3.85 (m, 2H), 3.95 (m, 2H), 6.10 (s, 2H), 7.71 (s, 1H), 11.45 (s, 1H)
Reaction SMILES: [CH2:1]([C:3]1[N:4]=[C:5]2[C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[O:19][CH3:20])=[N:9][CH:8]=[CH:7][N:6]2[C:21]=1[C:22](O)([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:20][O:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[C:10]1[C:5]2[N:6]([C:21](/[C:22](/[CH2:26][CH2:27][CH3:28])=[CH:23]\[CH2:24][CH3:25])=[C:3]([CH2:1][CH3:2])[N:4]=2)[CH:7]=[CH:8][N:9]=1
Reactant: CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
Temperature: 25 °C
Reaction time: 1 h
Yield: 101.4 %

Procedure:
4-[2-Ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazin-3-yl]-4-heptanol (115 mg, 0.29 mmol) and triethylamine (0.48 mL, 3.5 mmol) were dissolved in methylene chloride (3 mL), then methanesulfonyl chloride (0.13 mL, 1.7 mmol) was added thereto under ice-cooling, and the mixture was stirred at room temperature for 1 hour. An aqueous saturated sodium bicarbonate solution was added to the reaction mixture, which was extracted with ethyl acetate and evaporated. The resulting residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1) to give the title compound (111 mg) as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]3[CH:15]=[CH:16][O:17][C:13]=3[C:12]([CH3:18])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C(Cl)(Cl)(Cl)Cl.C1C(=O)N(Br)C(=[O:27])C1.OP([O-])([O-])=O.[K+].[K+]>CC(N=NC(C#N)(C)C)(C#N)C.CC#N>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:14]3[CH:15]=[CH:16][O:17][C:13]=3[C:12]([CH:18]=[O:27])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ccc(-c2ccc(C)c3occc23)cc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=P([O-])([O-])O
Agent: [K+]
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: COc1ccc(-c2ccc(C=O)c3occc23)cc1
Yield: 78.7 %

Procedure:
To a 250 ml round bottom flask was added 4-(4-methoxyphenyl)-7-methylbenzofuran (600 mg, 2.52 mmol), CCl4 (70 ml), NBS (490 mg, 2.77 mmol), and a catalytic amount of AIBN (25 mg). The reaction was brought to reflux for 2 h after which the reaction was allowed to cool, the solids were filtered off, and the solution concentrated. CH3CN (30 ml), K2HPO4 (440 mg, 2.53 mmol), and potassium benzeneselenite (630 mg, 2.77 mmol) were added and the reaction was brought to reflux for 2 h after. The reaction was cooled, passed through a silica plug (washed with 30% EtOAc/hex.), and concentrated to 810 mg of an orange solid. Further purification by chromatography (100% CH2Cl2) afforded 500 mg (78%) of product as a tan colored solid: mp 104–105° C.; 1H NMR (500 MHz, DMSO-d6): δ 3.85 (3H, s), 7.14 (2H, d, J=8.8 Hz), 7.20 (1H, d, J=2.2 Hz), 7.56 (1H, d, J=8.0 Hz), 7.69 (2H, d, J=8.8 Hz), 7.91 (1H, d, J=7.7 Hz), 8.26 (1H, d, J=2.2 Hz), 10.36 (1H, s); HRMS (ESI+) m/z 253.08622 ([M+H]+).
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([CH:21]=[CH:22][CH:23]=2)[CH2:9][NH:10][C:11]2[C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=[C:13](Cl)[CH:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[NH2:24][C:25]1[CH:35]=[CH:34][C:28]([C:29]([N:31]([CH3:33])[CH3:32])=[O:30])=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:1]1([C:6]2[CH:7]=[C:8]([CH:21]=[CH:22][CH:23]=2)[CH2:9][NH:10][C:11]2[C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=[C:13]([NH:24][C:25]3[CH:26]=[CH:27][C:28]([C:29](=[O:30])[N:31]([CH3:32])[CH3:33])=[CH:34][CH:35]=3)[CH:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CN(C)C(=O)c1ccc(N)cc1
Reactant: NC(=O)c1cnc(Cl)cc1NCc1cccc(-n2ccnc2)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CN(C)C(=O)c1ccc(Nc2cc(NCc3cccc(-n4ccnc4)c3)c(C(N)=O)cn2)cc1
Reaction time: 3 h
Yield: 9 %

Procedure:
A mixture of 4-(3-(1H-imidazol-1-yl)benzylamino)-6-chloronicotinamide (56 mg, 0.170 mmol), 4-amino-N,N-dimethylbenzamide (42 mg, 0.256 mmol), Cs2CO3 (110 mg, 0.337 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 120 C for 3 h. The mixture was concentrated in vacuo, the residue was purified by HPLC to give the titled compound (7 mg). MS 456.3 (M+H); UV 257.8 nm; t 0.344 min.
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1.[SH:26][CH:27](O)[CH3:28].B(F)(F)F>O1CCCC1>[S:26]1[C:2]2([CH2:3][CH2:4][N:5]([C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]4=[O:24])=[CH:10][C:9]=3[F:25])[CH2:6][CH2:7]2)[O:1][CH2:28][CH2:27]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(=O)CC3)c(F)c2)C(=O)O1
Reactant: CC(O)S
Agent: FB(F)F
Solvent: C1CCOC1
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCC4(CC3)OCCS4)c(F)c2)C(=O)O1
Yield: 85 %

Procedure:
The mixture of (S)-N-{3-[4-(4-oxo-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (2.86 mmol), mercaptoethanol (3.15 mmol) and BF3 etherate (5.14 mmol) in 10 ml tetrahydrofuran was heated under reflux for 6 hours. The solvent was evaporated and the residue was extracted with ethyl acetate water mixture the organic layer was concentrated and the crude residue was purified on a silica gel column to afford the titled compound in 85% yield.
Reaction SMILES: [CH2:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([O:23]COC)=[C:6]([O:21][CH3:22])[CH:7]=[C:8]2/[C:13](/[CH3:20])=[CH:14]/[C:15]([O:17]CC)=[O:16])[CH3:2].[OH-].[K+].O.Cl>C(O)C.O1CCCC1>[CH2:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([OH:23])=[C:6]([O:21][CH3:22])[CH:7]=[C:8]2/[C:13](/[CH3:20])=[CH:14]/[C:15]([OH:17])=[O:16])[CH3:2]
Reactant: CCOC(=O)/C=C(\C)c1cc(OC)c(OCOC)c2c(CC)cccc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: CCc1cccc2c(/C(C)=C/C(=O)O)cc(OC)c(O)c12
Yield: 74.6 %

Procedure:
470 mg of ethyl (E)-3-(5-ethyl-3-methoxy-4-methoxymethoxy-1-naphthyl)-2-butenoate was dissolved in 5 ml of ethanol and 5 ml of tetrahydrofuran, to which 350 mg of potassium hydroxide and 2 ml of water were added, followed by refluxing for 1 hour. The reaction mixture was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated to obtain 280 mg of the titled compound as pale yellow crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([N:9]2[CH:14]([C:15]([O:17]CC)=[O:16])[CH:13]3[CH2:20][CH:10]2[CH2:11][CH2:12]3)=[O:8])=[CH:5][CH:4]=1.CO.[OH-].[Na+].Cl>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]2[CH:14]([C:15]([OH:17])=[O:16])[CH:13]3[CH2:20][CH:10]2[CH2:11][CH2:12]3)=[O:8])=[CH:21][CH:22]=1
Reactant: CCOC(=O)C1C2CCC(C2)N1C(=O)c1ccc(OC)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(C(=O)N2C3CCC(C3)C2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of ethyl 2-(4-methoxybenzoyl)-2-azabicyclo[2.2.1]heptane-3-carboxylate (239 mg, 0.787 mmol) in tetrahydrofuran (5 ml)-methanol (4 ml) was added 1N sodium hydroxide (5 ml), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated, to give 2-(4-methoxybenzoyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH2:15]1)(=[O:12])=[O:11])([O-])=O.O.O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][CH:14]1[CH2:15][CH2:16][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:18][CH2:19]1)(=[O:12])=[O:11]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)NC1CCN(Cc2ccccc2)CC1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1ccccc1S(=O)(=O)NC1CCN(Cc2ccccc2)CC1

Procedure:
To a solution of 75.0 g (0.2 mol) of 2-nitro-N-[1-(phenylmethyl)-4-piperidinyl]-benzenesulphonic acid amide in 2.0 l ethanol was added dropwise, at room temperature, a solution of 174.0 g ( 0.828 mol) of sodium dithionite-dihydrate in 700 ml of water. After the heat of the exothermic reaction had died away the mixture was refluxed for 4.5 hours, then the ethanol was distilled off and the aqueous phase remaining was extracted thoroughly with dichloromethane.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[N:16][N:15]=[CH:14]2.N.O1CCOCC1.C([N:37](C(C)C)CC)(C)C>S(Cl)(Cl)=O.CCOC(C)=O>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:37])=[O:7])=[CH:4][C:3]=1[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[N:16][N:15]=[CH:14]2
Reactant: CCN(C(C)C)C(C)C
Reactant: Cc1ccc(C(=O)O)cc1-c1ccc2c(N3CCOCC3)nncc2c1
Agent: N
Solvent: O=S(Cl)Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Cc1ccc(C(N)=O)cc1-c1ccc2c(N3CCOCC3)nncc2c1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
4-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid (86 mg, 0.25 mmol) was dissolved in thionyl chloride (3.6 mL) and heated to 70° C. for 2 h. The reaction mixture was concentrated in vacuo before ammonia, 0.5 M in 1,4-dioxane (10 mL, 4.9 mmol) and diisopropylethylamine (0.2 mL, 1.2 mmol) were added. The reaction mixture was heated to 50° C. for 5 h and stirred overnight at RT. The reaction was diluted with 100 mL of EtOAc, added to an addition funnel and partitioned with sodium bicarbonate (saturated, aqueous). The organic layers were washed 3 times 75 mL of sodium bicarbonate (saturated, aqueous), combined, dried over sodium sulfate, and concentrated via rotovap to give a crude product. The crude was purified by chromatography to obtain the title compound. Found MS (ES+): 349(M+H)+.