Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:10]1([CH3:19])[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+].O>CC1C=CC(C)=CC=1.N(CCO)(CCO)CCO.O.CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[C:13]1[CH:14]=[CH:15][C:10]([CH3:19])=[CH:11][CH:12]=1)#[N:5]
Reactant: Cc1ccc(B(O)O)cc1
Reactant: N#Cc1ccccc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccc(C)cc1
Solvent: CS(C)=O
Solvent: O
Product: Cc1ccc(-c2ccccc2C#N)cc1
Yield: 84.6 %

Procedure:
15 g of 2-chlorobenzonitrile, 14.8 g of p-tolueneboronic acid and 28.9 g of sodium carbonate in 50 ml of p-xylene, 40 ml of triethanolamine and 10 ml of water were heated to 120° C. At 80° C., a mixture of 24.7 mg of palladium acetate and 0.55 ml of TPPTS/H2O solution (0.6 molar) in 2.5 ml of DMSO was added. After the reaction was complete, the phases were separated. The aqueous phase was washed with 50 ml of toluene. The combined organic phases were washed with 20 ml of water and subsequently dried over sodium sulfate. Crystallization from n-heptane gave 17.8 g of 2-cyano-4'-methylbiphenyl.
Reaction SMILES: [C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:17][C@H:16]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:15][C@H:10]2[C:11](OC)=[O:12])=[O:8])=[CH:3][CH:2]=1.[BH4-].[Li+]>C1COCC1>[C:1]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:2]=[CH:3][C:4]([C:7]([N:9]2[CH2:17][C@H:16]([O:18][Si:19]([C:22]([CH3:23])([CH3:25])[CH3:24])([CH3:21])[CH3:20])[CH2:15][C@H:10]2[CH2:11][OH:12])=[O:8])=[CH:5][CH:6]=1
Reactant: COC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1C(=O)c1ccc(-c2ccccc2)cc1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)O[C@@H]1C[C@@H](CO)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Reaction time: 3 h

Procedure:
A solution of methyl (4R)-1-(1,1′-biphenyl-4-ylcarbonyl)-4-{[tert-butyl (dimethyl) silyl]oxy}-L-prolinate (intermediate 15a, 2.61 g, 5.94 mmol) in THF (60 ml) was cooled to 0° C. and treated with lithium borohydride (95%, 206 mg, 8.9 mmol). The reaction mixture was stirred for 3 h and quenched slowly with water. THF was removed under reduced pressure, the crude was redissolved in AcOEt, washed with sat. NH4Cl, brine, dried over magnesium sulfate, filtered and concentrated.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.O.OC1C2N=NNC=2C=CC=1.[CH2:25]([O:27][C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH2:30][NH2:31])[CH3:26].CCCCCC.C(OCC)(=O)C>CN(C=O)C.C(OCC)(=O)C>[CH2:25]([O:27][C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH2:30][NH:31][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[N:7][CH:6]=2)[N:1]=1)=[O:13])[CH3:26]
Reactant: O=C(O)c1ccc2cnccc2n1
Reactant: CCOc1ccccc1CN
Agent: Oc1cccc2[nH]nnc12
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1ccccc1CNC(=O)c1ccc2cnccc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.4 %

Procedure:
To a stirring mixture of 2-[1,6]naphthyridinecarboxylic acid (50 mg, 0.287 mmol) in anhydrous DMF (6.3 mL) at room temperature was added sequentially 1 hydroxybenzotriazole hydrate (42.7 mg, 0.316 mmol), 2-ethoxybenzyl amine (64.9 μL, 0.431 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (61.8 mg, 0.316 mmol). The resulting mixture was allowed to stir at room temperature overnight and it was found to be clear. The solvent was removed under vacuum and the resulting residue was redissolved in CH2Cl2 (50 mL). The organic layer was washed with aq. NaHCO3, dried over anhydrous Na2SO4, and concentrated to give the crude mixture. Flash column chromatography of the crude (50% hexane/ethyl acetate to 100% ethyl acetate) afforded the desired product as a white solid (85.0 mg, 96%): m.p. 79-80° C.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]1([C@H:17]2[CH2:22][CH2:21][N:20]([C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH2:19][C@@H:18]2[CH2:29][OH:30])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>ClCCl.C(N(CC)CC)C>[C:11]1([C@H:17]2[CH2:22][CH2:21][N:20]([C:23](=[O:28])[C:24]([F:26])([F:27])[F:25])[CH2:19][C@@H:18]2[CH:29]=[O:30])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(N1CC[C@H](c2ccccc2)[C@@H](CO)C1)C(F)(F)F
Agent: O=C(Cl)C(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: O=C[C@H]1CN(C(=O)C(F)(F)F)CC[C@@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 110.2 %

Procedure:
A solution of 1.37 mL of DMSO in 20 mL of dichloromethane was cooled to −78° C., and added dropwise 0.845 mL of oxalyl chloride (internal temperature −60° C. or lower). After stirring at the same temperature for 20 minutes, a solution of 1.46 g of rel-[(3R,4S)-4-phenyl-1-(trifluoroacetyl)piperidin-3-yl]methanol in 20 mL of dichloromethane was added dropwise thereto, followed by stirring for additional 20 minutes. 4.40 mL of triethylamine was added dropwise thereto, and the reaction temperature was then elevated to −30° C., followed by stirring for additional 15 minutes. To the reaction mixture was added a saturated ammonium chloride solution to stop the reaction, followed by warming to room temperature, and then extraction with chloroform. The organic layer was washed with water, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 1.597 g of rel-(3R,4S)-4-phenyl-1-(trifluoroacetyl)piperidine-3-carbaldehyde as a crude product.
Reaction SMILES: [C:1]([O:11][CH:12]([CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-])=O)=[CH:28][CH:27]=1)[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=1)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C>[Fe].O1CCOCC1>[C:1]([O:11][CH:12]([CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([NH2:21])=[CH:19][CH:20]=1)[CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(C=Cc1ccccc1)OC(COc1ccc([N+](=O)[O-])cc1)COc1ccc([N+](=O)[O-])cc1
Agent: [Fe]
Solvent: C1COCCO1
Product: Nc1ccc(OCC(COc2ccc(N)cc2)OC(=O)C=Cc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 8 h
Yield: 99.9 %

Procedure:
34.8 g (0.075 mole) of 1,3-bis(4-nitrophenoxy)-2-propyl cinnamate, 15 g of carbon black containing 5% Pt and 2% iron (product with water content of approximately 50%), and 300 ml of 1,4-dioxane were placed in a reaction vessel (hydrogenating apparatus). And stirring was conducted by heating at 60° C. under a hydrogen atmosphere. In approximately 8 hours, 10.8 L of hydrogen was absorbed and the reaction was completed when the absorption of hydrogen stopped. Then the reacted solution was separated by filtration for removing the catalyst and the filtrate was concentrated. 30.3 g of 1,3-bis(4-aminophenoxy)-2-propyl cinnamate was yielded. The exothermic peak temperature was 230° C.
Reaction SMILES: FC1C(N2CCC(C3C=CC=CN=3)CC2)=CC=C2C=1N(C1C=CC=CC=1C#N)N=C2C.[F:32][C:33]1[C:34](I)=[CH:35][CH:36]=[C:37]2[C:41]=1[N:40]([C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[C:45]#[N:46])[N:39]=[C:38]2[CH3:50].[N:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[N:58]1[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]1.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.O(C(C)(C)C)[Na]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:32][C:33]1[C:34]([N:61]2[CH2:62][CH2:63][N:58]([C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][N:52]=3)[CH2:59][CH2:60]2)=[CH:35][CH:36]=[C:37]2[C:41]=1[N:40]([C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45][NH2:46])[N:39]=[C:38]2[CH3:50]
Reactant: Cc1nn(-c2cccc(C#N)c2)c2c(F)c(I)ccc12
Reactant: c1ccc(N2CCNCC2)nc1
Agent: [Pd]
Agent: CC(C)(C)O[Na]
Agent: Cc1nn(-c2ccccc2C#N)c2c(F)c(N3CCC(c4ccccn4)CC3)ccc12
Product: Cc1nn(-c2cccc(CN)c2)c2c(F)c(N3CCN(c4ccccn4)CC3)ccc12
Yield: 35.5 %

Procedure:
3-[7-Fluoro-3-methyl-6-(3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-yl)-indazol-1-yl-benzonitrile: To a 5 ml round bottom flask equipped with magnetic stirrer, condenser, and argon inlet, 3-(7-fluoro-6-iodo-3-methyl-indazol-1-yl)-benzonitrile (189 mg, 0.5 mmole), 1-pyridin-2-yl piperazine (180 mg, 1.1 mmole), Pd2 (dba)3 (23 mg, 0.025 mmole), BINAP (31 mg, 0.050 mmole), NaO-t-Bu (69 mg, 0.70 mmole) were added. The reaction mixture was purged with argon for 10 minutes. Toluene (0.5 ml) was added. The reaction mixture was heated to reflux for 18 hrs. The reaction was partitioned with EtOAc, and filtered through Celite. The solvent was then removed under vacuum. The desired product (74 mg, 36% yield) was isolated via column chromatography with Hexanes/EtOAc (7/3) as eluent. 1H-NMR (400 MHz, CDCl3): δ 2.62 (s, 3H), 3.33 (t, J=4.93 Hz, 4H), 3.77 (t, J=4.93 Hz, 4H), 6.67-6.71 (m, 1 Hz), 6.74 (d, J=8.79 Hz, 1H), 7.03 (dd, J=8.36 Hz, 6.64 Hz, 1H), 7.44 (d, J=8.57 Hz, 1H), 7.52-7.57 (m, 1H), 7.58-7.65 (m, 2H), 7.86-7.91 (m, 1H), 7.93-7.96 (m, 1H), 8.24-8.26 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[C:4]1[C:9]([NH:10][CH:11]([CH:14]=O)[CH2:12][CH3:13])=[CH:8][C:7]([CH3:16])=[N:6][C:5]=1[O:17][C:18]1[C:23]([CH3:24])=[CH:22][C:21]([Cl:25])=[CH:20][C:19]=1[CH3:26].[CH3:28][NH2:29].[O-]S([O-])(=O)=O.[Na+].[Na+].[Na]>ClC(Cl)C.C(O)(=O)C>[CH3:1][O:2][C:3](=[O:27])[C:4]1[C:9]([NH:10][CH:11]([CH2:14][NH:29][CH3:28])[CH2:12][CH3:13])=[CH:8][C:7]([CH3:16])=[N:6][C:5]=1[O:17][C:18]1[C:23]([CH3:24])=[CH:22][C:21]([Cl:25])=[CH:20][C:19]=1[CH3:26]
Reactant: CN
Reactant: CCC(C=O)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C(=O)OC
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: CCC(CNC)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C(=O)OC
Temperature: 25 °C

Procedure:
A mixture of 2-(4-chloro-2,6-dimethyl-phenoxy)-4-(1-formyl-propylamino)-6-methyl-nicotinic acid methyl ester (67 mg, 0.17 mmol) in dichloroethane (2 ml) was treated with methylamine, 1 drop of acetic acid, anhydrous Na2SO4 and sodium cyanoborohdride and stirred at rt. overnight. The mixture was quenched with water, extracted with methylene chloride. The organic layer was separated, dried, concentrated, and purified by silica gel Biotage using methylene chloride to 5% methanol in methylene chloride as eluent to give the title compound as an off-white solid. 1HNMR(CDCl3) 8.07(d, 1H), 7.02(s, 2H), 6.29(s, 1H), 3.87(s, 3H), 3.80(m, 1H), 2.88(m, 2H), 2.56(s, 3H), 2.11(s, 3H), 2.06(s, 6H), 1.63(m, 2H), 0.99(t, 3H)ppm
Reaction SMILES: [CH3:1][O:2][C:3]1[NH:4][C:5](=[O:8])[NH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:15]1([C:21]2[CH:22]=[CH:23][C:24]([CH3:29])=[C:25]([CH:28]=2)[CH2:26]Br)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>C(#N)C>[CH3:1][O:2][C:3]1[N:4]([CH2:26][C:25]2[CH:28]=[C:21]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:22]=[CH:23][C:24]=2[CH3:29])[C:5](=[O:8])[NH:6][N:7]=1
Reactant: COc1n[nH]c(=O)[nH]1
Reactant: Cc1ccc(-c2ccccc2)cc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: COc1n[nH]c(=O)n1Cc1cc(-c2ccccc2)ccc1C
Reaction time: 5 h
Yield: 44.9 %

Procedure:
To a solution of 626 mg (5.44 mmol) of 5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (said compound is a known compound described in J. Chem. Soc. Perkin I, 2645 (1973) and this was produced according to the method described in this literature. In this literature, said compound is named as 3-methoxy-1,2,4-triazol-5(4H)-one) in 7 ml of dry acetonitrile was added 0.79 g (5.71 mmol) of potassium carbonate. To the mixture was added dropwise a solution of 1.42 g (5.44 mmol) of 5-phenyl-2-methylbenzylbromide in 20 ml of dry acetonitrile at 55° C. After the mixture was stirred at the same temperature for additional 5 hours, water was added to the reaction mixture and it was extracted with ethyl acetate. The organic layer was washed with water, dried, and concentrated. To the resultant solid residue (1.51 g) was added tert-butyl methyl ether and the solid was washed and ice-cooled. The solid was collected by filtration and dried to obtain 0.72 g (2.44 mmol) of 5-methoxy-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one as white powder.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7].O.[C:34]([O-:37])([O-])=[O:35].[K+].[K+]>C1COCC1.CC(OC)(C)C>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:31])[F:32])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:34]([O:37][C:3]([CH3:4])([CH3:26])[CH3:2])=[O:35])[CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7]
Reactant: O=C(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)N1CCNC[C@H]1Cc1c[nH]c2ccccc12
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Solvent: COC(C)(C)C
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](Cc2c[nH]c3ccccc23)C1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
First 50 ml of a 55% by weight solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazine in THF and then 25 ml water were added to a suspension of 7.4 9 K2CO3 in 150 ml THF. A solution of 12.2 g tert. butoxycarbonyl anhydride in 50 ml THF was added to this receiving solution, and the mixture was stirred for 12 hours at room temperature. After reduction of the reaction mixture in a vacuum, the residue was taken up in 300 ml MTBE, and the organic phase was washed, in succession, twice with 100 ml portions of water, once with 50 ml of a 15% by weight aqueous tartaric acid solution and another four times with 100 ml portions of water, and then dried over sodium sulfate/SiO2. After filtering out the drying agent, the filtrate was reduced in a vacuum, and the residue was taken up in 20 ml MTBE. After heating to 60° C., 120 ml ligroin was added, and the volume was then reduced by approximately 100 ml by vacuum distillation. After another addition of 100 ml ligroin, the mixture was left to stand for 3 days to precipitate. The precipitated solid was filtered out, washed three times more with 30 ml portions of ligroin and dried at 60° C. in a vacuum. 82.0 g of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl]-4-(tert.butoxycarbonyl)piperazine were obtained as a solid, melting point 155-156° C.
Reaction SMILES: [CH3:1][C:2]([CH:6]1[CH2:11][CH2:10][O:9][C:8]([CH3:13])([CH3:12])[O:7]1)([CH3:5])[CH:3]=C.P([O-])([O-])([O-])=[O:15]>C1COCC1.O=[Os](=O)(=O)=O>[CH3:12][C:8]1([CH3:13])[O:7][CH:6]([C:2]([CH3:1])([CH3:5])[CH:3]=[O:15])[CH2:11][CH2:10][O:9]1
Reactant: C=CC(C)(C)C1CCOC(C)(C)O1
Reactant: O=P([O-])([O-])[O-]
Agent: O=[Os](=O)(=O)=O
Solvent: C1CCOC1
Product: CC1(C)OCCC(C(C)(C)C=O)O1
Reaction time: 0.17 h
Yield: 76 %

Procedure:
286 mg (1.55 mmol) of acetonide 44 is dissolved in 18 ml of THF, and 14 ml of aqueous phosphate buffer at pH 7 is added. 400 μl (0.031 mol, 0.02 equivalent) of OsO4 solution (2.5% in tert-butanol) is added in drops to the reaction mixture that is stirred vigorously. After 10 minutes, 996 mg (4.656 mmol, 3 equivalents) of NalO4 is added in portions over a period of 20 minutes. The mixture is stirred vigorously at room temperature and, after 24 and 48 hours in each case, another 332 mg (1.55 mmol, 2×1.0 equivalents each) of NalO4 is added. After 55 hours, the phases are separated, the aqueous phase is extracted with ether, the combined organic phases are dried on MgSO4 and concentrated by evaporation. The residue is purified by column chromatography with pentane:DE=1:1. 221 mg (1.19 mmol) of aldehyde 45 corresponding to a yield of 76% is obtained.
Reaction SMILES: Cl.[N+](C1C=CC(NC(NC(=N)CCCC)=O)=CC=1)([O-])=O.Cl.[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35](=[NH:42])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[S:33])=[CH:27][CH:26]=1)([O-])=O>>[NH2:22][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35](=[NH:42])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[S:33])=[CH:27][CH:26]=1
Reactant: CCCCCCC(=N)NC(=S)Nc1ccc([N+](=O)[O-])cc1
Agent: CCCCC(=N)NC(=O)Nc1ccc([N+](=O)[O-])cc1
Agent: Cl
Product: CCCCCCC(=N)NC(=S)Nc1ccc(N)cc1

Procedure:
By following a procedure similar to that described in Example 10 but substituting for 1-(4-nitrophenyl)-3-(pentanimidoyl)urea hydrochloride an equivalent amount of 1-(4-nitrophenyl)-3-(heptanimidoyl)-2-thiourea hydrochloride there is obtained 1-(4-aminophenyl)-3-(heptanimidoyl)-2-thiourea.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)#[CH:2].Cl[C:10](=[N:16][OH:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12].C(N(CC)CC)C>ClC(Cl)C.C[C]1[C](C)[C](C)[C](C)[C]1C.C1CC=CCCC=C1.Cl[Ru]>[C:3]1([C:1]2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:16][O:17][CH:2]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C#Cc1ccccc1
Reactant: CCOC(=O)C(Cl)=NO
Agent: Cl[Ru]
Agent: C1=C\CC/C=C\CC/1
Agent: C[C]1[C](C)[C](C)[C](C)[C]1C
Solvent: CCN(CC)CC
Solvent: CC(Cl)Cl
Solvent: C1=CCCC=CCC1
Product: CCOC(=O)c1nocc1-c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 5.1 %

Procedure:
Ethynylbenzene (0.300 mL; 2.73 mmol) and ethyl 2-chloro-2-(hydroxyimino)acetate (0.455 g; 3.00 mmol) were dissolved in degassed dichloroethane (15 mL), chloro(1,5-cyclooctadiene)(pentamethylcyclopentadienyl)ruthenium (II) (0.052 g; 0.136 mmol) and triethyl amine (0.476 mL; 3.41 mmol) were added and the resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was then filtered through a pad of silica gel and the filtrate was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica (eluent 2 to 20% ethyl acetate in heptane) and by preparative HPLC method 3 to yield 0.030 g (5%) of the title compound as a solid.
Reaction SMILES: [Cl-].[OH:2][NH3+:3].[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]=O)=[CH:7][CH:6]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(Cl)Cl>[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]=[N:3][OH:2])=[CH:7][CH:6]=1
Reactant: [NH3+]O
Reactant: O=CCc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: ON=CCc1ccc(F)cc1
Reaction time: 48 h
Yield: 90.8 %

Procedure:
113 g of hydroxylammonium chloride in 300 ml of water are added to 160 g of p-fluorophenylacetaldehyde in 500 ml of methylene chloride. A solution of 87 g of sodium carbonate in 300 ml of water is slowly added dropwise to the stirred mixture at room temperature, and the reaction is allowed to continue for 2 days. The organic phase is separated off, washed with water, dried over Na2SO4 and filtered, and the filtrate is freed from the solvent. 161 g of p-fluorophenylacetaldoxime of melting point 113°-115° C. are obtained. 200 MHz NMR spectrum in CDCl3 : ##STR10## (cis/trans isomer mixture=1:1)
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH3:15])[CH:10]=2)[C:6]([CH3:16])=[CH:5][C:3]=1N.N(OCCC(C)C)=O.C(I)[I:26]>>[F:1][C:2]1[C:3]([I:26])=[CH:5][C:6]([CH3:16])=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH3:15])[CH:10]=2)[CH:8]=1
Reactant: Cc1cc(-c2cc(F)c(N)cc2C)ccn1
Reactant: ICI
Agent: CC(C)CCON=O
Product: Cc1cc(-c2cc(F)c(I)cc2C)ccn1
Temperature: 100 °C
Reaction time: 0.33 h

Procedure:
To the solution of 2-fluoro-5-methyl-4-(2-methylpyridin-4-yl)aniline 191-3 (1.02 g, 4.7 mmol) in CH2I2 (16 mL) was added isoamyl nitrite (6 mL) slowly at −10° C. After 20 minutes, the reaction was heated to 100° C. for 2 hours. The solvent was removed by rotary evaporation and the residue was dissolved in ethyl acetate and washed with Na2S2O5, brine and taken to dryness by rotary evaporation. The residue was purified by silica gel flash chromatography, eluted with 40% ethyl acetate in hexane to give 4-(5-fluoro-4-iodo-2-methylphenyl)-2-methylpyridine 191-4. MS m/z 328.10 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[CH2:7][C:8]([CH3:13])([CH3:12])[O:9]2)=[CH:4][CH:3]=1.Cl>CO.[Zn]>[CH3:12][C:8]1([CH3:13])[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=2)[O:9]1
Reactant: CC1(C)CC(=O)c2ccc(O)cc2O1
Agent: Cl
Agent: [Zn]
Solvent: CO
Product: CC1(C)CCc2ccc(O)cc2O1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 62.6 %

Procedure:
A mixture of 7-hydroxy-2,2-dimethylchroman-4-one (500 mg, 2.60 mmol) and HCl (conc. 10 mL) in MeOH (30 mL) was stirred at 0° C. for 10 min, then zinc power (300 mg) was added slowly. After stirring at room temperature for 16 hrs, the solvents were removed under reduced pressure and the mixture was extracted with EtOAc (150×3 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase column falsh (28%-35% MeCN in 0.5% NH4HCO3) to give target product of 2,2-dimethylchroman-7-ol (290 mg, 62%) as a brown yellow solid. LCMS (ESI) m/z: 177.1 [M−H]+; 1H-NMR (500 MHz, CDCl3): δ 6.89 (d, J=8.0 Hz, 1H), 6.34 (dd, J=8.5, 2.5 Hz, 1H), 6.27 (d, J=2.5 Hz, 1H), 4.70 (s, 1H), 2.69 (t, J=13.5, 7.0 Hz, 2H), 1.77 (t, J=13.5, 7.0 Hz, 2H), 1.32 (s, 6H).
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[N:18]=[C:19]([NH:36][C:37]4[CH:38]=[C:39]([S:43]([NH2:46])(=[O:45])=[O:44])[CH:40]=[CH:41][CH:42]=4)[C:20]4[CH:25]=[CH:24][N:23](S(C5C=CC(C)=CC=5)(=O)=O)[C:21]=4[N:22]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[OH-].[K+]>CO>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17]3[N:18]=[C:19]([NH:36][C:37]4[CH:38]=[C:39]([S:43]([NH2:46])(=[O:44])=[O:45])[CH:40]=[CH:41][CH:42]=4)[C:20]4[CH:25]=[CH:24][NH:23][C:21]=4[N:22]=3)=[CH:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCN(c2ccc(Nc3nc(Nc4cccc(S(N)(=O)=O)c4)c4ccn(S(=O)(=O)c5ccc(C)cc5)c4n3)cc2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CC(=O)N1CCN(c2ccc(Nc3nc(Nc4cccc(S(N)(=O)=O)c4)c4cc[nH]c4n3)cc2)CC1
Temperature: 60 °C
Yield: 45.3 %

Procedure:
To a solution of 3-(2-(4-(4-acetylpiperazin-1-yl)phenylamino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzenesulfonamide (40 mg, 0.061 mmol) in MeOH (3 mL), aq. 1N KOH (1.0 mL, 1.0 mmol) was added. The mixture was heated at 60° C. for 3 h. It was concentrated in vacuo. The residue was acidified with HOAc (1 mL) before being purified by HPLC to give 3-(2-(4-(4-acetylpiperazin-1-yl)phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzenesulfonamide (14 mg), MS 507.1 (M+H); UV 212.0, 282.9, 313.8 nm; and 3-(2-(4-(piperazin-1-yl)phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzenesulfonamide (4 mg), MS 465.1 (M+H); UV 203.8, 281.7 nm.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][C:8]1[C:13]([NH2:14])=[CH:12][N:11]=[CH:10][N:9]=1.[N:15]([CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]1)=[C:16]=[S:17]>O1CCCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][C:8]1[C:13]([NH:14][C:16]([NH:15][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)=[S:17])=[CH:12][N:11]=[CH:10][N:9]=1
Reactant: Nc1cncnc1NCc1ccco1
Reactant: CCOC(=O)N1CCC(N=C=S)CC1
Solvent: C1CCOC1
Product: CCOC(=O)N1CCC(NC(=S)Nc2cncnc2NCc2ccco2)CC1
Reaction time: 48 h
Yield: 96.2 %

Procedure:
A mixture of 42.5 parts of N4 -(2-furanylmethyl)-4.5-pyrimidinediamine, 50.5 parts of ethyl 4-isothiocyanato-1-piperidinecarboxylate and 630 parts of tetrahydrofuran was stirred for 48 hours at reflux temperature. After cooling, the product was filtered off, washed with tetrahydrofuran and 1,1'-oxybisethane and dried, yielding 86.4 parts (96.2%) of ethyl 4-[[[[4-[(2-furanylmethyl)amino]-5-pyrimidinyl]amino]thioxomethyl]-amino]-1-piperidinecarboxylate (interm. 31).