Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[C:11]([C:20]([F:23])([F:22])[F:21])=[CH:10][C:9]=1[NH2:24])([CH3:4])([CH3:3])[CH3:2].C([O:30][C:31](=O)[CH2:32][C:33]([C:35]1[CH:40]=[CH:39][N:38]=[C:37]([C:41]#[N:42])[CH:36]=1)=[O:34])(C)(C)C>>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]([F:18])([F:17])[F:19])[C:11]([C:20]([F:22])([F:23])[F:21])=[CH:10][C:9]=1[NH:24][C:31](=[O:30])[CH2:32][C:33]([C:35]1[CH:40]=[CH:39][N:38]=[C:37]([C:41]#[N:42])[CH:36]=1)=[O:34])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1ccnc(C#N)c1
Reactant: CC(C)(C)OC(=O)Nc1cc(OCC(F)(F)F)c(C(F)(F)F)cc1N
Product: CC(C)(C)OC(=O)Nc1cc(OCC(F)(F)F)c(C(F)(F)F)cc1NC(=O)CC(=O)c1ccnc(C#N)c1

Procedure:
The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example J21) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light brown solid (262 mg).
Reaction SMILES: ClCCl.[CH2:4]([S:11][C:12]1[S:13][C:14]2[CH:20]=[C:19]([F:21])[C:18]([N:22]3[C:26](=[O:27])[N:25]([CH3:28])[C:24]([CH3:29])=[N:23]3)=[CH:17][C:15]=2[N:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.ClC1C=C(C=CC=1)C(OO)=[O:35]>O>[CH2:4]([S:11]([C:12]1[S:13][C:14]2[CH:20]=[C:19]([F:21])[C:18]([N:22]3[C:26](=[O:27])[N:25]([CH3:28])[C:24]([CH3:29])=[N:23]3)=[CH:17][C:15]=2[N:16]=1)=[O:35])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1nn(-c2cc3nc(SCc4ccccc4)sc3cc2F)c(=O)n1C
Solvent: O
Solvent: ClCCl
Product: Cc1nn(-c2cc3nc(S(=O)Cc4ccccc4)sc3cc2F)c(=O)n1C
Reaction time: 0.17 h
Yield: 91 %

Procedure:
10 mL of dichloromethane was charged with 0.001 mol 1-(2-(benzylthio)-6-fluorobenzo[d]thiazol-5-yl)-3,4-dimethyl-1H-1,2,4-triazol-5(4H)-one. The mixture was stirred for 10 mins and then 0.0011 mol m-chloroperoxybenzoic acid (MCPBA) were added. After stirring at room temperature for 2 hours, the mixture was poured into 30 mL of water, extracted with 15 mL dichloromethane twice. Organic phases were combined and dried over anhydrous sodium sulfate. Filtration and removal of solvent under vacuum gave the title compound as a white solid in a 91% yield.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:15]=[CH:14][C:8]([CH2:9][NH:10][C:11]([NH2:13])=[S:12])=[CH:7][CH:6]=1)=[O:4].Br[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)=O.C(=O)(O)[O-].[Na+].O>C(#N)C.CCCCCC>[N+:26]([C:23]1[CH:24]=[CH:25][C:20]([C:18]2[N:13]=[C:11]([NH:10][CH2:9][C:8]3[CH:14]=[CH:15][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[S:12][CH:17]=2)=[CH:21][CH:22]=1)([O-:28])=[O:27]
Reactant: COC(=O)c1ccc(CNC(N)=S)cc1
Reactant: O=C(CBr)c1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: CCCCCC
Solvent: O
Product: COC(=O)c1ccc(CNc2nc(-c3ccc([N+](=O)[O-])cc3)cs2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.9 %

Procedure:
To a suspension of 1-(4-methoxycarbonylbenzyl)-2-thiourea (138.0 g, 0.554 mol) obtained in Example 1(1) in acetonitrile (1380 ml, 10.0 v/w) were successively added 2-bromo-4′-nitroacetophenone (124.1 g, 0.554 mol) and sodium bicarbonate (46.9 g, 0.559 mol), and the mixture was heated under reflux for 2 hr. After cooling to room temperature, water (1380 ml, 10.0 v/w) and n-hexane (690 ml, 5.0 v/w) were successively added and the mixture was stirred for 1 hr. The precipitated crystals were collected by filtration, washed successively with water (1000 ml) and n-hexane (500 ml) and dried in vacuo to give the title compound (183.9 g, yield 89.9%) as a yellow solid.
Reaction SMILES: [CH2:1](Br)[C:2]#[CH:3].C1(C)C=CC=CC=1.[C:12]([O:16][C:17]([NH:19][C@@H:20]([CH2:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[C@@H:21]([O:24][Si:25]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])[CH:22]=[O:23])=[O:18])([CH3:15])([CH3:14])[CH3:13].[NH4+].[Cl-]>C(OCC)C.Cl[Hg]Cl>[C:12]([O:16][C:17]([NH:19][C@@H:20]([CH2:35][CH:36]1[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]1)[C@@H:21]([O:24][Si:25]([CH:26]([CH3:27])[CH3:28])([CH:29]([CH3:30])[CH3:31])[CH:32]([CH3:33])[CH3:34])[C@@H:22]([OH:23])[CH2:3][C:2]#[CH:1])=[O:18])([CH3:13])([CH3:14])[CH3:15]
Reactant: CC(C)[Si](O[C@@H](C=O)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C)(C(C)C)C(C)C
Reactant: C#CCBr
Agent: Cl[Hg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: C#CC[C@H](O)[C@H](O[Si](C(C)C)(C(C)C)C(C)C)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C
Temperature: 10 °C
Reaction time: 0.75 h

Procedure:
To a dry flask under an N2 atmosphere was added Mg (0.40 g, 6.4 mmol), HgCl2 (0.03 g) and anhydrous diethyl ether (4 mL). A solution of 80% propargyl bromide in toluene (1.83 mL, 16.4 mmol) was added to an addition funnel and several drops were added to the reaction mixture. After the reaction was initiated, anhydrous diethyl ether (10 mL) was added to the reaction flask and anhydrous diethyl ether (10 mL) was added to the funnel solution. The funnel solution was added dropwise while the reaction solution was cooled with a 10° C. bath. The white, opaque mixture was stirred at room temperature for 45 minutes and then a solution of aldehyde of Step 4 (2.05 g, 4.64 mmol) in anhydrous diethyl ether (10 mL) was added dropwise. The yellow, opaque mixture was stirred at room temperature for 2 hours. The mixture was cooled to about 0° C. with an ice-water bath and a saturated NH4Cl solution (25 mL) was added dropwise. The organic layer was collected and the aqueous layer was extracted with diethyl ether (10 mL). The combined organic layers were washed with H2O (10 mL) and brine and then dried over MgSO4. The filtrate was concentrated and purified by medium pressure column chromatography (10% EtOH in hexane, silica gel, Rf 0.20) to give the title compound as a clear, pale yellow liquid (1.49 g, 65% yield). The 1H and 13C NMR spectral data were consistent with the proposed structure.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:41][C:42]1[CH:47]=[CH:46][C:45](O)=[CH:44][CH:43]=1>C1COCC1>[Br:41][C:42]1[CH:47]=[CH:46][C:45]([O:21][CH2:20][CH2:19][C:16]2[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=2)=[CH:44][CH:43]=1
Reactant: OCCc1ccncc1
Reactant: Oc1ccc(Br)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Brc1ccc(OCCc2ccncc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 53.1 %

Procedure:
Diethyl azodicarboxylate (4.44 mL, mmol, 40%) was slowly added to a solution of 2-pyridin-4-yl-ethanol (1.00 g, 8.12 mmol), triphenylphosphine (2.56 g, 9.74 mmol), and 4-bromophenol (1.40 g, 8.12 mmol) in THF (40.6 mL) at 0° C. under nitrogen. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with water (150 mL) and extracted with ethyl acetate (200 mL). The organics were washed with 1N aqueous NaOH (100 mL) and brine (100 mL). The organics were dried (Na2SO4), filtered, and concentrated. The crude material was crystallized with ether:heptanes (1:1, ˜25 mL) and the solid was removed via filtration and washed with ether:heptanes. The combined filtrates were concentrated and further purified via flash chromatography using an Analogix SF25-40 g column and ethyl acetate in heptane (0-30%) as the eluant to afford the title compound as a clear liquid (1.20 g, 46.2%). LC-MS m/z 278.4 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.11 (t, 2H) 4.19 (t, J=6.44 Hz, 2H) 6.77 (d, J=8.98 Hz, 2H) 7.22-7.26 (m, 2H) 7.38 (d, J=4.69 Hz, 2H) 8.54-8.57 (m, 3H)
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.[NH2:16][C:17]1[CH:22]=[C:21]([Cl:23])[C:20]([OH:24])=[C:19]([Cl:25])[CH:18]=1>>[Cl:23][C:21]1[CH:22]=[C:17]([NH2:16])[CH:18]=[C:19]([Cl:25])[C:20]=1[O:24][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: Nc1cc(Cl)c(O)c(Cl)c1
Reactant: FC(F)(F)Oc1ccc2nc(Cl)sc2c1
Product: Nc1cc(Cl)c(Oc2nc3ccc(OC(F)(F)F)cc3s2)c(Cl)c1

Procedure:
3,5-Dichloro-4-(6-trifluoromethoxy-benzothiazol-2-yloxy)-phenylamine was synthesized (76%) from 2-chloro-6-trifluoromethoxybenzotiazole (413) and 4-amino-2,6-dichlorophenol (Aldrich) in a similar manner as described in Example 417.
Reaction SMILES: [I-].C([NH:4][C:5]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:6]=1[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N+:10]=1[CH3:15])=O.[I-].[N+](C1C=CC=CC=1C=CC1C=CC=C[N+]=1C)([O-])=O>Cl>[NH2:4][C:5]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:6]=1[CH2:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]1[CH3:15]
Reactant: COc1ccc(NC=O)c(CCc2cccc[n+]2C)c1
Agent: C[n+]1ccccc1C=Cc1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: [I-]
Product: COc1ccc(N)c(CCC2CCCCN2C)c1

Procedure:
Catalytic reduction of 2-(2-formamido-5-methoxyphenethyl)-1-methylpyridinium iodide as described in Example 1 for 2-(o-nitrostyryl)-1-methylpyridinium iodide provides 2-(2-formamido-5-methoxyphenethyl)lmethylpiperidine. This material is deformylated in 1 N methanolic hydrogen chloride providing 2-(2-amino-5-methoxyphenethyl)-1-methylpiperidine.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2.[Br:13]Br>ClCCl>[Br:13][C:7]1[C:6]2[C:11](=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=2)[C:10](=[O:12])[NH:9][CH:8]=1
Reactant: BrBr
Reactant: Cc1cccc2cc[nH]c(=O)c12
Solvent: ClCCl
Product: Cc1cccc2c(Br)c[nH]c(=O)c12
Reaction time: 1 h
Yield: 108.1 %

Procedure:
To a solution of 8-methyl-2H-isoquinolin-1-one (1.15 g) in dichloromethane (20 ml) was added dropwise a solution of bromine (1.26 g) in dichloromethane (4 ml) at room temperature. The mixture was stirred at the same temperature for one hour, and the solvent was evaporated under reduced pressure. The residue was crystallized from ether to give 4-bromo-8-methyl-2H-isoquinolin-1-one (1.86 g) as colorless crystals. APCI-Mass m/Z 238/240 (M+H). (2) The above 4-bromo-8-methyl-2H-isoquinolin-1-one was treated in a manner similar to Reference Example 2 to give the target compound as colorless crystals. APCI-Mass m/Z 356/358M+H).
Reaction SMILES: [CH2:1]=[C:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][CH2:3]1.[OH-:18].[Na+].OO>C1COCC1>[CH2:11]([O:10][CH2:9][CH2:8][C@H:5]1[CH2:6][CH2:7][C@H:2]([CH2:1][OH:18])[CH2:3][CH2:4]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: [OH-]
Reactant: C=C1CCC(CCOCc2ccccc2)CC1
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Product: OC[C@H]1CC[C@H](CCOCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a cooled (0 C) solution of ((2-(4-methylenecyclohexyl)ethoxy)methyl)benzene (9.68 g, 41.66 mmol) in THF (200 mL) was added B2H6 Me2S complex (2M in THF, 41.66 mL, 83.32 mmol) under N2. After being stirred at 0° C. for 2 h and at rt for another 2 h, the solution was cooled to 0° C. and added a mixture of 3M aqueous NaOH solution (34 ml) and 30% hydrogen peroxide solution (34 mL) dropwise. The resulting mixture was stirred at 0° C. for 1 h and at rt for 1.5 h. Aqueous workup and purification by flash column chromatography (eluent: 40% EtOAc in hexanes) gave the product as yellow oil (7.04 g, 68%). LC/MC: 249.1 (MH)+.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]([O:12][CH2:13][CH3:14])[C:9]([O:15][CH3:16])=[CH:8][C:3]=1[C:4](OC)=[O:5].Cl.[CH:18](N)=[NH:19]>C(N)=O>[CH2:13]([O:12][C:10]1[CH:11]=[C:2]2[C:3]([C:4](=[O:5])[NH:19][CH:18]=[N:1]2)=[CH:8][C:9]=1[O:15][CH3:16])[CH3:14]
Reactant: CCOc1cc(N)c(C(=O)OC)cc1OC
Reactant: N=CN
Agent: Cl
Solvent: NC=O
Product: CCOc1cc2nc[nH]c(=O)c2cc1OC
Temperature: 130 °C
Yield: 69.8 %

Procedure:
A mixture of methyl 2-amino-4-ethoxy-5-methoxybenzoate (4.43 g, 19.7 mmol) and formamidine hydrochloride (2.255 g, 28 mmol) in formamide (20 mL) was heated at 130° C. for 8 hours. The reaction mixture was quenched with water, filtered, washed with water, and dried under vacuum with P2O5 to give 7-ethoxy-6-methoxyquinazolin-4(3H)-one as solid (3.029 g, 70%). 1H NMR (300 MHz, DMSO-d6) δ 12.1 (br, 1H), 7.97 (s, 1H), 7.43 (s, 1H), 7.10 (s, 1H), 4.16 (q, 2H), 3.87 (s, 3H), 1.38 (t, 3H); LC-MS (ESI) m/z 221 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]([OH:12])=[O:11].[CH2:13](N(CC)CC)[CH3:14].Cl.C(N=C=NCCCN(C)C)C.N1(C2C=CN=CC=2)CCCC1.C(O)C>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: O=C(O)Cc1c(Cl)cccc1Cl
Reactant: CCN(CC)CC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: c1cc(N2CCCC2)ccn1
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)Cc1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.6 %

Procedure:
To a solution of 2,6-dichlorophenyl acetic acid (6.7 g, 0.033 mol) in dichloromethane (170 ml) was added triethylamine (5.9 ml, 0.043 mol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (8.1 g, 0.043 mol) and 4-pyrrolidinopyridine (0.58 g, 0.004 mol). Ethanol (2.5 ml, 0.043 mol) was added dropwise and the solution stirred overnight at room temperature. After this time the mixture was washed with water (2×100 ml), 1M HCl (2×100 ml), aq. K2CO3 (sat.; 2×100 ml) and brine (100 ml). The organic phase was separated, dried (Na2SO4) and evaporated. The residue was chromatographed on silica, using petrol:ether (10:1) as the eluant, to give the ester (7.2 g, 94%) as a colourless oil which solidified on standing at 0° C. 1H NMR (360 MHz, d6 -DMSO) δ 1.26 (3H, t, J=7.1 Hz), 4.01 (2H, s), 4.18 (2H, q, J=7.1 Hz), 7.15 (1H, t, J=8.6 Hz), 7.32 (2H, d, J=8.6 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:22](=[NH:23])[N:21]([CH2:24][CH3:25])[C:14]3[N:15]=[C:16]([S:19][CH3:20])[N:17]=[CH:18][C:13]=3[CH:12]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>COC(C)(C)C>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([C:11]2[C:22](=[N:23][C:26](=[O:28])[CH3:27])[N:21]([CH2:24][CH3:25])[C:14]3[N:15]=[C:16]([S:19][CH3:20])[N:17]=[CH:18][C:13]=3[CH:12]=2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: CC(=O)OC(C)=O
Reactant: CCn1c(=N)c(-c2cc(OC)cc(OC)c2)cc2cnc(SC)nc21
Solvent: COC(C)(C)C
Product: CCn1c(=NC(C)=O)c(-c2cc(OC)cc(OC)c2)cc2cnc(SC)nc21
Yield: 78 %

Procedure:
A mixture of the product of Example 4, 6-(3,5-dimethoxy-phenyl)-8-ethyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-ylideneamine (50.0 g, 0.145 mol), and acetic anhydride (150 mL) were heated with stirring until reflux at which point all the starting material dissolved. The reaction mixture was heated at reflux for 5 minutes, cooled in an ice bath, and t-butyl methyl ether added. The product was collected by filtration, washed with acetic anhydride (50 mL) and ether (100 mL) to afford 43.7 g (78% yield) of the titled compound. mp 145–150° C.
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH:5]1[CH2:9][CH2:8][CH2:7][C:6]1=O)#[N:2].[NH3:11].[H][H]>>[N:2]12[CH2:1][CH2:3][CH2:4][CH:5]1[CH2:6][CH2:7][CH2:8][CH2:9]2.[NH2:2][CH2:1][CH2:3][CH2:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH:6]1[NH2:11]
Reactant: N#CCCC1CCCC1=O
Reactant: [H][H]
Reactant: N
Product: C1CCN2CCCC2C1
Product: NCCCC1CCCC1N

Procedure:
Through a tubular reactor (diameter 16 mm, packing height 50 cm, oil-heated double jacket), installed up-stream of the hydrogenation reactor and packed with 67.2 g (96 ml) of γ-aluminum oxide in the form of 1.5 mm extrudates, there were pumped upwardly, per hour, 11.0 g of 2-(2-cyanoethyl)-cyclopentanone (purity 77.0%, 0.062 mole) and 535 ml of liquid ammonia (321 g, 18.9 moles) at a pressure of 250 bar and a temperature of 70° C. Hydrogen was then added to the stream at a rate of 60 standard liters (2.7 moles) per hour, and the effluent from the in-line imination reactor was passed upwardly through the hydrogenation reactor at a pressure of 250 bar and a temperature of 120° C. The product obtained after an on-stream period of 45.4 hours was worked up by fractional distillation. There were obtained 91.2 g of 1-azabicyclo[4.3.0]nonane (b.p.=80° C./ 50 mm Hg) and 224.4 g of 2-(3-aminopropyl)-cyclopentylamine (b.p.=122° C./28 mm Hg)l. The yield of 2-(3-aminopropyl)-cyclopentylamine was 56.3% of theory.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:14])=[C:4]2[C:10]([N+:11]([O-])=O)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CC(O)C>C1COCC1.[Pt]>[Cl:1][C:2]1[C:3]([F:14])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: O=[N+]([O-])c1c[nH]c2ncc(Cl)c(F)c12
Agent: [Pt]
Solvent: CC(C)O
Solvent: C1CCOC1
Product: Nc1c[nH]c2ncc(Cl)c(F)c12
Reaction time: 20 h
Yield: 108.1 %

Procedure:
5-Chloro-4-fluoro-3-nitro-1H-pyrrolo[2,3-b]pyridine (1.00 g, 4.6 mmol) and platinum-0.5% Fe (0.452 g, 0.06 mmol) were suspended in THF (12.4 mL) with IPA (6.2 mL). The mixture was hydrogenated at 20 psi for 20 hours, and then the catalyst was removed by filtration. The filtrate was concentrated to dryness, and 5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (923 mg, 107% yield) was isolated as a solid.
Reaction SMILES: [CH:1]([CH:3]=[O:4])=O.S(=O)=[O:6].N.[NH2:9][CH2:10][C:11]([OH:13])=[O:12]>>[NH:9]([CH2:1][C:3]([OH:4])=[O:6])[CH2:10][C:11]([OH:13])=[O:12]
Reactant: NCC(=O)O
Reactant: O=CC=O
Reactant: O=S=O
Agent: N
Product: O=C(O)CNCC(=O)O

Procedure:
Using the apparatus and procedure of Example 6, two runs were carried out in which glyoxal was reacted with sulfur dioxide and ammonia. In the first run, one equivalent of sulfur dioxide and one equivalent of glyoxal were charged per mole of ammonia. In the second run, two moles of glyoxal and two moles of sulfur dioxide were charged per mole of ammonia. In each run a mixture of glycine and iminodiacetic acid was produced. The results of the runs of this example are set forth in Table III.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[C:9]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[C:9]1[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCCc1c(-c2ccccc2)n(Cc2ccccc2)c2ccc(-c3ccc(OC)cc3)cc12
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCCCCc1c(-c2ccccc2)n(Cc2ccccc2)c2ccc(-c3ccc(O)cc3)cc12

Procedure:
The desired product was prepared using a procedure similar to step 4 of example 3. Thus, 1-benzyl-5-(4-methoxy-phenyl)-3-pentyl-2-phenyl-1H-indole (0.708 g, 1.54 mmol) was reacted with BBr3 (1.9 ml of a 1M solution in CH2Cl2) to give the product (0.609 g, 1.367 mmol, 89%) as a viscous oil. 1H NMR (DMSO-d6) δ 0.76 (t, J=69 Hz, 3H), 1.13-1.22 (m, 4H), 1.53-1.59 (m, 2H), 2.67 (t, J=7.3 Hz, 2H), 5.26 (s, 2H), 6.82-6.85 (m, 4H), 7.14 (t, J=7.2 Hz, 1H), 7.19 (t, J=6.9 Hz, 2H), 7.29-7.37 (m, 4H), 7.41-7.49 (m, 5H), 7.70 (d, J=1.2 Hz, 1H), 9.37 (s, 1H); [ESI(+)], m/z 446 (M+H)+;
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][SH:9])[CH2:3][CH2:2]1.[Na].C1(C)C=CC=CC=1.Br[CH2:19][C:20](=[O:42])[C@@H:21]1[C@:38]2([CH3:39])[C@H:24]([C@H:25]3[C@H:35]([C:36](=[O:40])[CH2:37]2)[C@:33]2([CH3:34])[C@H:28]([CH2:29][C@H:30]([OH:41])[CH2:31][CH2:32]2)[CH2:27][CH2:26]3)[CH2:23][CH2:22]1>C(O)(C)C>[OH:41][C@@H:30]1[CH2:31][CH2:32][C@@:33]2([CH3:34])[C@@H:28]([CH2:27][CH2:26][C@@H:25]3[C@@H:35]2[C:36](=[O:40])[CH2:37][C@@:38]2([CH3:39])[C@H:24]3[CH2:23][CH2:22][C@@H:21]2[C:20](=[O:42])[CH2:19][S:9][CH2:8][CH2:7][N:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)[CH2:29]1
Reactant: C[C@]12CC[C@@H](O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)CBr)[C@@]3(C)CC(=O)[C@@H]12
Reactant: SCCN1CCOCC1
Agent: [Na]
Solvent: Cc1ccccc1
Solvent: CC(C)O
Product: C[C@]12CC[C@@H](O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)CSCCN4CCOCC4)[C@@]3(C)CC(=O)[C@@H]12
Reaction time: 0.08 h

Procedure:
2-Morpholinoethanethiol (1 ml.) was added to a warm solution of sodium (0.6 g.) in a mixture of dry toluene (30 ml.) and isopropyl alcohol (25 ml.). After 5 min., 21-bromo-3α-hydroxy-5α-pregnane-11,20-dione (2.0 g.) was added and the resulting mixture was stirred at 40° for 30 min. The mixture was then partitioned between water and ether and the organic layer was washed with water, dried (Na2SO4) and evaporated. The residue was subjected to preparative t.l.c. (EtOAc) to give title compound (150 mg.) as a white foam, [α]D + 73° (c 0.9); λmax. 243 nm. (ε 570).
Reaction SMILES: [CH3:1][C@@:2]1([CH2:12][OH:13])[C@@H:4]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[O:3]1.[Si:14](OS(C(F)(F)F)(=O)=O)([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16].N1C(C)=CC(C)=CC=1C.[Si](O[C@H](CCC)[C@@H](C)C=O)(C(C)(C)C)(C)C>>[CH2:15]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[O:3][C@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C@H:2]([CH3:1])[CH:12]=[O:13])[CH3:16]
Reactant: CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F
Reactant: C[C@]1(CO)O[C@@H]1Cc1ccccc1
Agent: CCC[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)C=O
Solvent: Cc1cc(C)nc(C)c1
Product: CC[Si](CC)(CC)O[C@H](Cc1ccccc1)[C@H](C)C=O
Yield: 80 %

Procedure:
Epoxy alcohol 10, 1.2 eq of TESOTf, and 1.5 eq of collidine were reacted as in the preparation of 16 give 80% of aldehyde 11. 1H NMR (CDCl3, 500.35 MHz) δ:9.64 (1H, d J=0.77 Hz), 7.30-7.05 (5H,m) 4.37 (1H, J=3.06, 10.40 Hz), 2.76 (1H, d J=6.64 Hz), 2.75 (2H, d J=7.42 Hz), 2.27 (1H, qdd, J=7.00, 3.38, 0.77 Hz), 1.10 (3H, d, J=7.04 Hz), 0.95-0.75 (6H, m), 0.6-0.4 (9H, m). 1H NMR integration of δ 9.64 to the contaminant δ 9.71 indicated a 93.6:6.4 ratio.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[OH-].[Na+].O1CCCC1.Cl>O.C(O)C>[F:25][C:2]([F:1])([F:26])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[O:13][C:12]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(-c3ccc(C(F)(F)F)cc3)o2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)c1ccc(-c2ccc(-c3ccc(C(F)(F)F)cc3)o2)cc1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 84.9 %

Procedure:
A mixture of ethyl 4-[5-(4-trifluoromethylphenyl)-2-furyl]benzoate (1.80 g), 1 M aqueous sodium hydroxide solution (15 ml), tetrahydrofuran (50 ml) and ethanol (50 ml) was stirred at 60° C. for 1.5 hrs. After cooling, the reaction mixture was poured into water, and 1 M hydrochloric acid (40 ml) was added. The crystals were collected by filtration and recrystallized from ethanol to give 4-[5-(4-trifluoromethylphenyl)-2-furyl]benzoic acid (1.41 g, yield 85%) as a colorless crystalline powder. melting point: 270–271° C.
Reaction SMILES: C[O:2][C:3](=[O:54])[C@H:4]([CH2:6][C:7]([C:10](=[O:53])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][CH2:18][C:19]2[N:20]=[CH:21][N:22]([C:24]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:23]=2)[C:12]=1[C:43]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45][CH:44]=1)([CH3:9])[CH3:8])[NH2:5].[Li+].[OH-]>C1COCC1.O>[C:24]([N:22]1[CH:23]=[C:19]([CH2:18][NH:17][C:13]2[C:12]([C:43]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[CH:46]=[CH:45][CH:44]=3)=[C:11]([CH:16]=[CH:15][CH:14]=2)[C:10]([C:7]([CH3:9])([CH3:8])[CH2:6][C@@H:4]([C:3]([OH:54])=[O:2])[NH2:5])=[O:53])[N:20]=[CH:21]1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: COC(=O)[C@@H](N)CC(C)(C)C(=O)c1cccc(NCc2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)c1-c1cccc2ccccc12
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C[C@H](N)C(=O)O)C(=O)c1cccc(NCc2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)c1-c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The compound of Example 388A (0.24 g, 0.34 mmoles) was dissolved in 10 mL of THF/H2O (2:1) and LiOH (0.029 g, 0.68 mmoles) was added. The reaction was stirred at room temperature for 2 h. The THF was evaporated and the residue dissolved in 15 mL water, and 1N HCl added to lower the pH to 2. The compound is then extracted with ethyl acetate (3×25 mL), dried and the solvents evaporated to afford the free carboxylic acid as a white solid. (0.20 g, 84%).