Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:4][C@H:5]2[CH2:10][CH2:9][C@H:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[CH3:25][O:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][CH:28]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>C(Cl)Cl>[CH:1]1([N:4]([C@H:5]2[CH2:10][CH2:9][C@H:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:7][CH2:6]2)[C:31](=[O:32])[C:30]2[CH:34]=[CH:35][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)[CH2:2][CH2:3]1
Reactant: COc1ccc(C(=O)O)cc1
Reactant: COC(=O)C[C@H]1CC[C@H](NC2CC2)CC1
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C[C@H]1CC[C@H](N(C(=O)c2ccc(OC)cc2)C2CC2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 2-(trans-4-(cyclopropylamino)cyclohexyl)acetate (0.150 g, 0.710 mmol) in CH2Cl2 (2.5 mL) were added diisopropylethylamine (0.173 ml, 0.994 mmol), 4-methoxybenzoic acid (0.130 g, 0.852 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.470 g, 1.85 mmol) sequentially. The mixture was stirred at room temperature overnight, diluted with CH2Cl2 (50 mL), and then washed with 10% Na2CO3 and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified through silica gel chromatography eluting with 18%-25% EtOAc-hexane. The desired amide product was obtained as a colorless oil (0.174 g). MS: 346 (M+1), C20H27NO4.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Br:10])[C:3]=1[CH2:11][CH2:12][C:13]([O:15]C(C)(C)C)=[O:14]>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Br:10])[C:3]=1[CH2:11][CH2:12][C:13]([OH:15])=[O:14]
Reactant: COc1cc(Br)c(CCC(=O)OC(C)(C)C)c(Br)c1
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(Br)c(CCC(=O)O)c(Br)c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a solution of t-butyl 3-(2,6-dibromo-4-methoxyphenyl)-propionate (1.32 g) in 3.6 mL of an isole was added 20 mL of trifluoroacetic acid dropwise. The resulting mixture was stirred for 20 min at room temperature, then concentrated. The resulting residue was redissolved in 20 mL of EtOAc and extracted with 40 mL of pH 4 buffer solution. The aqueous phase was extracted with 2×20 mL of EtOAc and the combined resulting organics were washed with 20 mL of brine, dried over MgSO4, and concentrated to yield 3-(2,6-dibromo-4-methoxyphenyl)-propionic acid as a pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.09 (s, 2H); 3.77 (s, 3H); 3.27 (m, 2H); 2.62 (m, 2H).
Reaction SMILES: [N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:38]=[C:37]([N+:39]([O-])=O)[CH:36]=[CH:35][C:34]=3[O:42][CH3:43])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1>CCO.[Pd]>[NH2:39][C:37]1[CH:36]=[CH:35][C:34]([O:42][CH3:43])=[C:33]([C:8]2[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])=[N:10][C:5]([N:1]3[CH2:4][CH2:3][CH2:2]3)=[CH:6][CH:7]=2)[CH:38]=1
Reactant: COc1ccc([N+](=O)[O-])cc1-c1ccc(N2CCC2)nc1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
Agent: [Pd]
Solvent: CCO
Product: COc1ccc(N)cc1-c1ccc(N2CCC2)nc1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C

Procedure:
To a solution of (4S,5R)-3-{[6-azetidin-1-yl-3-(2-methoxy-5-nitrophenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (1.26 g, 2.064 mmol) in EtOH (80 mL) was added Pd—C (10%) (0.220 g, 0.206 mmol). The mixture was subjected to hydrogenation by using a Hz balloon for 6.5 h. The mixture was filtered through Celite® and the filtrate was concentrated in vacuo. This was purified by flash chromatography (Biotage Horizon, 40M, Si, ˜30 mL/min, 100% hexanes for 260 mL, gradient to 50% EtOAc in hexanes over 2240 mL) to afford (4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=580.2. found=581.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.86 (s, 1H); 7.75 (s, 2H); 7.32 (d, J=8.3 Hz, 1H); 6.79 (d, J=8.6 Hz, 1H); 6.68 (dd, J=8.6, 2.9 Hz, 1H); 6.54 (d, 2.9 Hz, 1H); 6.27 (d, J=8.3 Hz, 1H); 5.61 (d, J=8.5 Hz, 1H); 4.93-4.30 (m, 1H); 4.18-4.01 (m, 6H); 3.70 (s, 3H); 3.51 (s, br, 2H); 2.46-2.37 (m, 2H); 0.68 (s, br, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[C:12]([Si:14]([CH3:17])([CH3:16])[CH3:15])#[CH:13]>CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:15][Si:14]([CH3:17])([CH3:16])[C:12]#[C:13][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2
Reactant: Brc1ccc2cnccc2c1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccc2cnccc2c1
Temperature: 50 °C
Reaction time: 1 h
Yield: 101.7 %

Procedure:
To a solution of 6-bromoisoquinoline (2.0 g, 9.6 mmol) (commercially available from Gateway Chemical Technology, Inc.) in 45 mL of Et3N was added PdCl2(PPh3)2 (0.34 g, 0.48 mmol) and copper(I) iodide (0.27 g, 1.4 mmol). The mixture was degassed by bubbling nitrogen through the mixture for 1 minute. Ethynyltrimethylsilane (2.7 mL, 19 mmol) was added. The mixture was heated to 50° C. After 1 hour, the solvent was removed by rotary evaporation and the residue was purified by flash chromatography on silica gel (5% to 30% EtOAc/hexanes), affording 6-(2-(trimethylsilyl)ethynyl)isoquinoline (2.2 g, 100% yield).
Reaction SMILES: C1(C)C=CC(S([N:10]2[CH2:16][CH:15]([N:17]([CH3:19])[CH3:18])[CH2:14][N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:12][CH2:11]2)(=O)=O)=CC=1.C1(O)C=CC=CC=1.Br>C(O)(=O)C>[CH3:18][N:17]([CH:15]1[CH2:14][NH:13][CH2:12][CH2:11][NH:10][CH2:16]1)[CH3:19]
Reactant: Cc1ccc(S(=O)(=O)N2CCN(S(=O)(=O)c3ccc(C)cc3)CC(N(C)C)C2)cc1
Agent: Br
Solvent: CC(=O)O
Solvent: Oc1ccccc1
Product: CN(C)C1CNCCNC1
Reaction time: 6 h
Yield: 241.9 %

Procedure:
Weighed out to a reaction vessel was 250 mg (0.56 mmol) of 1,4-bis(p-toluenesulfonyl)-6-(N,N-dimethylamino)-hexahydro-1,4-diazepine synthesized by the above process, and 0.20 ml (2.3 mmol) of phenol and a 30% acetic acid solution (4 ml) of hydrobromic acid were added, followed by stirring for 6 hours in a bath controlled to 70° C. After the reaction mixture was concentrated under reduced pressure, diethyl ether (5 ml) was added to the residue with stirring, and a supernatant was removed. This process was repeated twice to remove diethyl ether-soluble material. The residue was concentrated again under reduced pressure to completely remove diethyl ether. Ethanol (2 ml) was added to the resultant residue, and the mixture was stirred for 30 minutes. Diethyl ether (2 ml) was added to the resultant solution, and the mixture was cooled in an ice bath, thereby obtaining 194 mg (yield: 91%) of the title compound as a colorless crystalline powder (melting point: 245° C., decomposed).
Reaction SMILES: C1(N[N:8]=[C:9]([C:11]2[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:13][O:14][C:15]=2[CH3:16])[CH3:10])C=CC=CC=1>O>[CH3:16][C:15]1[O:14][N:13]=[C:12]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:11]=1[C:9]1[NH:8][C:17]2[C:22]([CH:10]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2
Reactant: CC(=NNc1ccccc1)c1c(-c2ccccc2)noc1C
Solvent: O
Product: Cc1onc(-c2ccccc2)c1-c1cc2ccccc2[nH]1
Reaction time: 3 h

Procedure:
To 1350 grams of polyphosphoric acid at 100° to 110° C., there is added portionwise 89.3 g (0.307 mole) of 1-(5-methyl-3-phenyl-4-isoxazolyl)-1-ethanone phenyl hydrazone, while maintaining the temperature between 105° and 115° C. After addition is complete the mixture is stirred at 100° to 110° C. for 3 hours. The mixture is then poured onto ice and water and the resulting solid is filtered and washed with water. The solid is then dissolved in ether, washed with water, dried and evaporated partially and cooled in ice. The resulting solid is filtered and washed with cold ether to give 2-(5-methyl-3-phenyl-4-isoxazolyl)-indole; m.p. 145° to 146° C.
Reaction SMILES: CO[C:3]1[C:4](=[O:17])[C:5]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][CH:7]=[CH:8][CH:9]=1.[NH3:18]>CO>[NH2:18][C:3]1[C:4](=[O:17])[C:5]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COc1ccccc(Oc2ccccc2)c1=O
Reactant: N
Solvent: CO
Product: Nc1ccccc(Oc2ccccc2)c1=O
Temperature: 80 °C

Procedure:
A solution of 2-methoxy-7-phenoxy-2,4,6-cycloheptatrien-1-one (2.0 g, described above) in methanol (30 ml) is cooled to -25° C and saturated with gaseous ammonia. The mixture is heated in a pressure bottle at 80° C for 4 hours and cooled to -70° C. The bottle is opened and the solvent is removed under reduced pressure. The residue is crystallized from ethyl acetate to give 2-amino-7-phenoxy-2,4,6-cycloheptatrien-1-one.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1)=[O:3].[C:11]([O:15][CH3:16])(=[O:14])[CH:12]=[CH2:13].C(=O)(O)[O-].[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:2]([C:4]1[CH:9]=[CH:8][C:7](/[CH:13]=[CH:12]/[C:11]([O:15][CH3:16])=[O:14])=[CH:6][CH:5]=1)(=[O:3])[CH3:1]
Reactant: C=CC(=O)OC
Reactant: CC(=O)c1ccc(Br)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Solvent: CN(C)C=O
Product: COC(=O)/C=C/c1ccc(C(C)=O)cc1
Temperature: 130 °C
Yield: 76.8 %

Procedure:
To 4-bromoacetophenone (1 g, 5 mmol) in anhydrous DMF (30 mL) were added methyl acrylate (450 μL, 5 mmol), sodium bicarbonate (420 mg, 5 mmol) tetrabutylammonium bromide (1.61 g, 5 mmol) and palladium acetate (56 mg, 0.25 mmol) and the reaction mixture was heated at 130° C. for 2 h. The DMF was removed by concentration under reduced pressure, the crude was dissolved in EtOAc (100 mL) and washed with water (100 mL) then brine (100 mL). The organic layer was dried (MgSO4), filtered and concentrated under vacuum to afford the crude product. This was purified by flash chromatography (1:1 heptane/EtOAc) to yield the desired product (784 mg, 77%). m/z=205 [M+H]+; 1H NMR (300 MHz, CDCl3) δ: 7.99 (2H, d, J=8.3 Hz), 7.73 (1H, d, J=16.2 Hz), 7.63 (2H, d, J=8.3 Hz), 6.55 (1H, d, J=16.0 Hz), 3.85 (3H, s), 2.64 (3H, s).
Reaction SMILES: C([O:4][C:5]([C:7]1[N:8]([N:12]([C:18](=[O:37])[CH2:19][C:20]2[NH:25][C:24]3[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:23]=3[S:22](=[O:36])(=[O:35])[CH:21]=2)[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:9]=[CH:10][CH:11]=1)=O)C=C.[O-]CC.[Na+].Cl>C(O)C>[OH:4][C:5]1[C:7]2[N:8]([CH:9]=[CH:10][CH:11]=2)[N:12]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[C:18](=[O:37])[C:19]=1[C:20]1[NH:25][C:24]2[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:23]=2[S:22](=[O:35])(=[O:36])[CH:21]=1
Reactant: C=CCOC(=O)c1cccn1N(CCC(C)C)C(=O)CC1=CS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CC(C)CCn1c(=O)c(C2=CS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)c(O)c2cccn21
Temperature: 60 °C
Reaction time: 4 h
Yield: 13.3 %

Procedure:
Crude 1-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-1H-pyrrole-2-carboxylic acid allyl ester (Example 16a, 0.3 mmol) was dissolved in ethanol (3 mL). A 21% solution of sodium ethoxide in ethanol (0.448 mL, 1.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h. Upon cooling to 25° C., the mixture was poured into 1.0 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. Purification by flash column chromatography (Teledyne Isco RediSep; 20% ethyl acetate in hexanes to 100% ethyl acetate in hexanes) afforded the desired product, N-{3-[4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-methanesulfonamide (20 mg, 0.04 mmol, 13% yield over two steps) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ: 1.05 (6H, d, J=6.6 Hz), 1.64-1.81 (3H, m), 3.11 (3H, s), 4.24-4.31 (2H, m), 5.53 (1H, s), 6.41-6.46 (1H, m), 6.97-7.10 (3H, m), 7.30-7.33 (1H, m), 7.60-7.64 (1H, m), 7.70-7.72 (1H, m). LC-MS (ESI) calcd for C21H24N4O6S2 492.11. found 493.3 [M+H+].
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[NH:11][CH:12]=[C:13]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][C:18]([O:26][CH3:27])=[C:19]([O:24][CH3:25])[CH:20]=2)[N:15]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:14]1[CH3:33].C1(CNC=C2C(=O)C3C(=CC(OC)=C(OC)C=3)N(C(OCC)=O)C2C)C2C(=CC=CC=2)C=CC=1.C1(CCNC=C2C(=O)C3C(=CC(OC)=C(OC)C=3)N(C(OCC)=O)C2C)C2C(=CC=CC=2)C=CC=1.C1(C(NC=C2C(=O)C3C(=CC(OC)=C(OC)C=3)N(C(OCC)=O)C2C)CC)C2C(=CC=CC=2)C=CC=1.C1(C(CC)CNC=C2C(=O)C3C(=CC(OC)=C(OC)C=3)N(C(OCC)=O)C2C)C2C(=CC=CC=2)C=CC=1>>[C:2]1([NH:11][CH:12]=[C:13]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][C:18]([O:26][CH3:27])=[C:19]([O:24][CH3:25])[CH:20]=3)[N:15]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:14]2[CH3:33])[C:1]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNc2ccc3ccccc3c2)C1C
Agent: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNC(CC)c2cccc3ccccc23)C1C
Agent: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNCC(CC)c2cccc3ccccc23)C1C
Agent: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNCCc2cccc3ccccc23)C1C
Product: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNc2cccc3ccccc23)C1C

Procedure:
3-(β-naphthylaminomethylene)-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester; 3-(α-naphthylmethylaminomethylene)-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester; 3-(β-naphthylethylaminomethylene)-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester; 3-(α-naphthylpropylaminomethylene)-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester; and 3-(β-naphthylbutylaminomethylene)-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]2[CH2:13][N:14]([C:16]3[C:17]([CH3:33])=[C:18]([CH3:32])[C:19]4[N:20]([CH:22]=[C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)[N:24]=4)[N:21]=3)[CH2:15][CH:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:34]Cl.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl.CO>[CH2:1]([N:8]1[CH2:12][CH:11]2[CH2:13][N:14]([C:16]3[C:17]([CH3:33])=[C:18]([CH3:32])[C:19]4[N:20]([C:22]([I:34])=[C:23]([C:25]5[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=5)[N:24]=4)[N:21]=3)[CH2:15][CH:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(N2CC3CN(Cc4ccccc4)CC3C2)nn2cc(-c3ccc(F)cc3)nc2c1C
Reactant: ClI
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1c(N2CC3CN(Cc4ccccc4)CC3C2)nn2c(I)c(-c3ccc(F)cc3)nc2c1C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution, cooled to 0° C., of 3.2 g (7.3 mmol) of 6-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2-yl)-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazine in 20 mL of chloroform is added dropwise a solution of 1.8 g (11 mmol) of iodine monochloride in 3 mL of methanol and the medium is stirred for one hour at room temperature. The medium is then basified by addition of aqueous sodium hydrogen carbonate solution and 5% sodium thiosulfate solution is then added until the medium has decolorized.
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-:3])=[O:2].N[C:21]1[C:34]2[C:33](=[O:35])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26](=[O:36])[C:25]=2[CH:24]=[CH:23][CH:22]=1.[S-2].[K+].[K+].[OH2:40]>>[NH2:1][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1.[OH:40][C:21]1[C:34]2[C:33](=[O:35])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26](=[O:36])[C:25]=2[CH:24]=[CH:23][C:22]=1[NH2:1].[N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O
Agent: Nc1cccc2c1C(=O)c1ccccc1C2=O
Agent: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Agent: [K+]
Product: Nc1ccc2c(c1O)C(=O)c1ccccc1C2=O

Procedure:
The manufacture of 1-aminoanthraquinones by the reduction of 1-nitroanthraquinone has already been described. Beisler, Jones, Am. Soc. 44, 2304, were able to reduce 1-nitroanthraquinone to 1-aminoanthraquinone by treatment with potassium sulphide in boiling water. On the other hand, 1-aminoanthraquinone and 1-hydroxy-aminoanthraquinone result side by side in the reduction of 1-nitroanthraquinone dissolved in benzene with NaHS in an aqueous calcium chloride solution (Haworth, Lapworth, Soc. 119, 774).
Reaction SMILES: C(N(S(F)(F)[F:7])CC)C.O[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[C:22](=[O:23])[CH:21]2[CH:19]([CH2:20]2)[C:18]1=[O:24].O>ClCCl>[F:7][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[C:22](=[O:23])[CH:21]2[CH:19]([CH2:20]2)[C:18]1=[O:24]
Reactant: CCN(CC)S(F)(F)F
Reactant: O=C1C2CC2C(=O)N1CCCCCCO
Solvent: O
Solvent: ClCCl
Product: O=C1C2CC2C(=O)N1CCCCCCF
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Diethylaminosulfurtrifluoride (76mg) was added dropwise to a stirred solution of 3-(6-hydroxyhex-1-yl)-3-azabicyclo[3.1.0]hexane-2,4-dione (from step (b), 100mg) in dichloromethane (2.0 ml) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred overnight at room temperature and water (3 ml) was then added. The reaction mixture was extracted with ether (2×10 ml) and the combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by chromatography on silica (5 g) using 40% ethyl acetate/hexane as eluant to give the title compound as a pale yellow oil.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[C:11]([F:23])=[C:12]([C:16]2[CH:17]=[N:18][C:19](Cl)=[N:20][CH:21]=2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.C1C[O:27][CH2:26][CH2:25]1.[O-]CC.[Na+].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CCOC(C)=O.O>[CH2:26]([O:27][C:19]1[N:20]=[CH:21][C:16]([C:12]2[C:11]([F:23])=[C:10]([CH2:9][OH:8])[CH:15]=[CH:14][CH:13]=2)=[CH:17][N:18]=1)[CH3:25]
Reactant: CC(C)(C)[Si](C)(C)OCc1cccc(-c2cnc(Cl)nc2)c1F
Reactant: C1CCOC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CC[O-]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: O
Product: CCOc1ncc(-c2cccc(CO)c2F)cn1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was mixed with THF (4 ml), and sodium ethoxide (132 mg) was added thereto, followed by stirring at room temperature for 3 hours, and then a 1M TBAF/THF solution (1.2 ml) was added thereto, followed by stirring at room temperature for 1 hour. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain [3-(2-ethoxypyrimidin-5-yl)-2-fluorophenyl]methanol (129 mg).
Reaction SMILES: [H-].[Na+].[NH2:3][C:4]1[N:9]=[CH:8][C:7]([CH2:10][CH:11]([C:17]2[N:18]=[CH:19][NH:20][CH:21]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:5]=1.Br[CH:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>CN(C=O)C>[NH2:3][C:4]1[N:9]=[CH:8][C:7]([CH2:10][CH:11]([C:17]2[N:18]=[CH:19][N:20]([CH:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:21]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:5]=1
Reactant: BrC(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)C(Cc1ccc(N)nc1)c1c[nH]cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(Cc1ccc(N)nc1)c1cn(C(c2ccccc2)c2ccccc2)cn1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
11 mg (0.23 mmol, 50%) of sodium hydride were added to a solution of 50 mg (0.19 mmol) of ethyl 3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propionate (example 1g) in 0.5 ml of DMF at RT and stirred for 1 h. Then 48 mg (0.19 mmol) of bromodiphenyl-methane were added, and the mixture was stirred at RT for 3.5 h. It was then heated at 60° C. for 2 h and, after cooling, 1 ml of water was added, the mixture was extracted with EA, and the organic phase was dried over Na2SO4, filtered and concentrated. Chromatography on silica gel afforded ethyl 3-(6-aminopyridin-3-yl)-2-(1-benzhydryl-1H-imidazol-4-yl)propionate. The product obtained in this way was taken up in 0.4 ml of 50% concentrated hydrochloric acid and treated in a microwave at 180° C. for 3 min. Freeze-drying after cooling of the reaction mixture afforded 5 mg of the title compound as bishydrochloride.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1.[NH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.C([BH3-])#N.[Na+]>CO>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:25][CH:24]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1
Reactant: O=Cc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Reactant: C1CCNCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: c1cnc2c(c1)CCCC2N(Cc1ccc(CN2CCCCC2)cc1)Cc1nc2ccccc2[nH]1
Reaction time: 5 h
Yield: 29.8 %

Procedure:
Using General Procedure A: To a stirred solution of 4-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzaldehyde (AMD9882) (144 mg, 0.36 mmol) in dry MeOH (5 mL) was added piperidine (0.040 mL, 0.40 mmol) and sodium cyanoborohydride (44 mg, 0.70 mmol) and the mixture stirred for 5 h. Purification of the crude product by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 50:1:1) afforded the desired adduct (50 mg, 30%) as a white foam.
Reaction SMILES: Br[CH:2]1[CH:6]([Br:7])[C:5]2[CH:8]=[C:9]([CH:12]=[O:13])[CH:10]=[CH:11][C:4]=2[O:3]1.[OH-].[K+]>C(O)C.O>[Br:7][C:6]1[C:5]2[CH:8]=[C:9]([CH:12]=[O:13])[CH:10]=[CH:11][C:4]=2[O:3][CH:2]=1
Reactant: O=Cc1ccc2c(c1)C(Br)C(Br)O2
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=Cc1ccc2occ(Br)c2c1
Temperature: 70 °C
Yield: 96.5 %

Procedure:
To a solution of 2,3-dibromo-2,3-dihydro-1-benzofuran-5-carbaldehyde (4.1 g) in dry ethanol (15 mL) was added a solution of KOH (2.2 eq.) in dry ethanol (14 mL) and refluxed at 70° C. for 1 h. The reaction mixture was cooled, diluted with water and extracted with EtOAc (3×50 mL). The organic layer was washed with water, brine and dried. The solvent was removed under vacuum and the residue was purified by flash chromatography (pet. ether/EtOAc 99.5:0.5) to give the title compound as a pale yellow solid (2.91 g (80% pure), yield=78%).