Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[CH:15]=[C:16]([S:18](Cl)(=[O:20])=[O:19])[S:17][C:11]=2[N:10]=[C:9]1[CH3:22].ClCCl.[C:26]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][NH2:34])(=[O:28])[CH3:27]>C(N(CC)CC)C>[C:26]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:34][S:18]([C:16]1[S:17][C:11]2[N:10]=[C:9]([CH3:22])[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:13](=[O:14])[C:12]=2[CH:15]=1)(=[O:20])=[O:19])(=[O:28])[CH3:27]
Reactant: CC(=O)NCCCCN
Reactant: Cc1nc2sc(S(=O)(=O)Cl)cc2c(=O)n1-c1ccccc1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)NCCCCNS(=O)(=O)c1cc2c(=O)n(-c3ccccc3Cl)c(C)nc2s1
Temperature: 25 °C
Reaction time: 3 h
Yield: 44.4 %

Procedure:
To 8.0 g of 3,4-dihydro-3-(2-chlorophenyl)-6-chlorosulfonyl-2-methyl-4-oxothieno[2,3-d]pyrimidine were added 150 ml of dichloromethane, 3.3 g of 4-acetylaminobutylamine and 5.9 ml of triethylamine, and the mixture was stirred at room temperature for 3 hours. After the reaction mixture was washed with water, the concentrated residue was purified by means of silica gel chromatography to obtain 5.71 g of oily substance, which was crystallized from ethyl acetate-hexane to afford 4.44 g of the title compound, m.p. 203°-206° C. (decomposition).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:24]=[CH:23][C:16]2[O:17][C@H:18]([CH2:21][OH:22])[CH2:19][O:20][C:15]=2[CH:14]=1.Cl([O-])=[O:26].[Na+].P([O-])(O)(O)=O.[Na+]>CC(=CC)C.O.C(O)(C)(C)C.C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:26])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:24]=[CH:23][C:16]2[O:17][C@H:18]([CH2:21][OH:22])[CH2:19][O:20][C:15]=2[CH:14]=1
Reactant: O=Cc1c[nH]c2cc(Cl)c(-c3ccc4c(c3)OC[C@@H](CO)O4)cc12
Reactant: [O-][Cl+][O-]
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: CC(C)(C)O
Product: O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc4c(c3)OC[C@@H](CO)O4)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 10.1 %

Procedure:
A mixture of 6-chloro-5-[(2R)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-1H-indole-3-carbaldehyde (1.0 g, 2.9 mmol), sodium chlorite (5.28 g, 58.3 mmol), sodium dihydrogen phosphate (9.06 g, 58.1 mmol) in 2-methyl-2-butene (10 mL), water (10 mL), t-butanol (10 mL) and acetonitrile (10 mL) was stirred overnight at room temperature. The mixture was quenched with saturated aqueous sodium bisulfite. Water (50 mL) and methylene chloride (50 mL) was added. The aqueous layer was extracted with methylene chloride (50 mL×3). The combined organic layer was dried over sodium sulfate, filtered and evaporated to give residue which was purified by reverse phase HPLC to give the title compound (105 mg, 14.3% yield).
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:22][C:23]2[CH:28]=[C:27]([C:29]#[N:30])[C:26]([Br:31])=[CH:25][C:24]=2[O:32][CH3:33])=[C:13](/[CH:15]=[CH:16]/[C:17]([O:19]CC)=O)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C[O-].[Na+]>C(Cl)Cl>[CH2:1]([S:8][C:9]1[CH:14]=[C:13]2[C:12](=[CH:11][CH:10]=1)[N:22]([C:23]1[C:24]([O:32][CH3:33])=[CH:25][C:26]([Br:31])=[C:27]([CH:28]=1)[C:29]#[N:30])[C:17](=[O:19])[CH:16]=[CH:15]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)/C=C/c1cc(SCc2ccccc2)ccc1Nc1cc(C#N)c(Br)cc1OC
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: COc1cc(Br)c(C#N)cc1-n1c(=O)ccc2cc(SCc3ccccc3)ccc21
Temperature: 80 °C
Yield: 90.9 %

Procedure:
A RBF was charged with (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-5-cyano-2-methoxyphenyl)amino)phenyl)acrylate (963 mg, 1.840 mmol) and MeOH (9199 μl) to give a thick, yellow suspension. Sodium methoxide (25 wt % in MeOH) (80 μl, 0.368 mmol) was added. A reflux condenser was attached, and the flask was heated to 80° C. overnight. In the morning, the mixture was diluted with DCM and concentrated. The residue was taken up in 2-PrOH, heated briefly to boiling, then sonicated for 20 s. The mixture was cooled then filtered. The collected solid was washed with 2-PrOH, then dried under a stream of N2 (g). The filtration was repeated with the filtrate. The two lots of material were combined to give 5-(6-(benzylthio)-2-oxoquinolin-1(2H)-yl)-2-bromo-4-methoxybenzonitrile (798 mg, 1.672 mmol, 91% yield) as a light-orange solid. m/z (ESI) 477.0 (M+H)+.
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[C:15]2[C:11](=[N:12][S:13][N:14]=2)[CH:10]=[CH:9][CH:8]=1)(C)C.C([O-])([O-])=O.[K+].[K+].C1COCC1>CO>[C:6]([C:7]1[C:15]2[C:11](=[N:12][S:13][N:14]=2)[CH:10]=[CH:9][CH:8]=1)#[CH:5]
Reactant: C[Si](C)(C)C#Cc1cccc2nsnc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Product: C#Cc1cccc2nsnc12
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
4-(Trimethylsilyl)ethynylbenzo[c][1,2,5]-thiadiazole (0.100 g, 4.30×10−4 mol), K2CO3 (78.6 mg, 5.71×10−4 mol), THF (3 ml), and MeOH (2 ml) were added to a 25-ml Schlenk tube. The mixture was purged with N2 for 5 min, following which the reaction was stirred at room temperature for 1.5 h. The reaction mixture was then filtered, evaporated, and chromatographed on silica gel using 5:1 hexanes:THF as the eluent. Yield=63 g (91.4% based on 0.100 g of 4-(trimethylsilyl)ethynylbenzothiadiazole). 1H NMR (500 MHz, CDCl3): δ 8.01 (m, 1H, Ph-H), 7.78 (m, 1H, Ph-H), 7.56 (m, 1H, Ph-H), 3.56 (s, 1H, —CC—H).
Reaction SMILES: [CH3:1][CH:2]([CH3:15])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11](Cl)=[CH:12][CH:13]=1)=[O:7].[N:16]1([C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>>[CH3:1][CH:2]([CH3:15])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11]([N:19]2[CH2:20][CH2:21][N:16]([C:22](=[O:23])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([F:33])([F:31])[F:32])[CH2:17][CH2:18]2)=[CH:12][CH:13]=1)=[O:7]
Reactant: CC(C)CCNC(=O)c1ccc(Cl)nn1
Reactant: O=C(c1ccccc1C(F)(F)F)N1CCNCC1
Product: CC(C)CCNC(=O)c1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 15, making variations only as required to use 6-chloropyridazine-3-carboxylic acid (3-methylbutyl)amide in place of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide to react with piperazin-1-yl-(2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (63.2% yield). 1H NMR (500 MHz, CDCl3) δ 8.05, 7.98, 7.75, 7.64, 7.57, 7.37, 7.00, 4.06, 3.89, 3.82-3.64, 3.49, 3.36, 1.70, 1.50, 0.95.
Reaction SMILES: [C:1]1([C:7]#[CH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1/[C:12](=[CH:20]/[C:21]1[NH:22][CH:23]=[CH:24][C:25]=1[O:26][CH3:27])/[C:13](=[O:19])[NH:14]2>[Cu]I.CN(C=O)C.CCN(CC)CC>[C:1]1([C:7]#[C:8][C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2/[C:12](=[CH:20]/[C:21]2[NH:22][CH:23]=[CH:24][C:25]=2[O:26][CH3:27])/[C:13](=[O:19])[NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(Br)c21
Reactant: C#Cc1ccccc1
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(C#Cc3ccccc3)c21

Procedure:
Using general Method D above, phenyl acetylene (32 mg, 0.31 mmol) (Aldrich) was coupled with (Z)-4-bromo-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (50 mg, 0.16 mmol) (Starting Material 1) using DPPFPdCl2 (6.5 mg) (Aldrich) and CuI (1.5 mg) (Aldrich) as catalyst in DMF (2 mL) and Et3N (3 mL) as solvent at 85° C. for 18 h, to yield (Z)-1,3-dihydro-4-(phenylethynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 20 mg, 37%)
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:17][C:18]([Cl:22])([Cl:21])[C:19]#[N:20]>C(OCC)C>[Cl:17][C:18]([Cl:22])([Cl:21])[C:19](=[NH:20])[O:9][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:10]1[CH:14]=[CH:13][S:12][CH:11]=1
Reactant: OC(c1ccc(Br)cc1)c1ccsc1
Reactant: N#CC(Cl)(Cl)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Product: N=C(OC(c1ccc(Br)cc1)c1ccsc1)C(Cl)(Cl)Cl
Temperature: 25 °C

Procedure:
To a solution of (4-bromophenyl)(thien-3-yl)methanol from step 1 (632 mg, 2.36 mmol) in diethyl ether (2.5 mL) at 0° C. was added sodium hydride (6 mg, 0.24 mmol). Then trichloroacetonitrile was added dropwise (237 μL, 2.36 mmol) over 15 minutes and the reaction was allowed to warm to room temperature for 3 hours. The reaction was then filtered over celite and concentrated under reduced pressure. The resulting crude compound was used as such in the next step.
Reaction SMILES: [K].[S:2]([C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8](O)=[O:9])(O)(=[O:4])=[O:3].C[N:16](C)C=O.C(Cl)(Cl)=O>C1(C)C=CC=CC=1>[S:2]1(=[O:4])(=[O:3])[C:6]2[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=2[C:8](=[O:9])[NH:16]1
Reactant: CN(C)C=O
Reactant: O=C(O)c1ccccc1S(=O)(=O)O
Agent: O=C(Cl)Cl
Agent: [K]
Solvent: Cc1ccccc1
Product: O=C1NS(=O)(=O)c2ccccc21
Temperature: 80 °C

Procedure:
Into a four necked flask equipped with a stirrer, a thermometer, a condenser and a phosgene inlet, were charged 24.0 g (0.1 mole) of the monopotassium salt of o-sulfobenzoic acid ##STR10## 150 ml of toluene and 0.22 g (0.003 mole) of dimethylformamide. The mixture was stirred at 80° C and 23 g of phosgene were introduced into the mixture over 4 hours. The reaction was continued by maintaining the temperature at 80° - 90° C under refluxing with stirring for 3 hours. After the reaction, nitrogen gas was injected into the mixture to remove excess phosgene. The reaction mixture was filtered to remove potassium chloride and the filtrate was condensed and a colorless condensate was obtained.
Reaction SMILES: C([O:3][CH2:4][CH2:5][C:6]1[C:7]2[N:8]([N:19]=[CH:20][N:21]=2)[C:9]([NH2:18])=[N:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)C.B(Cl)(Cl)Cl.ClCCl>O>[OH:3][CH2:4][CH2:5][C:6]1[C:7]2[N:8]([N:19]=[CH:20][N:21]=2)[C:9]([NH2:18])=[N:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CCOCCc1c(-c2ccccc2)nc(N)n2ncnc12
Agent: ClB(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: Nc1nc(-c2ccccc2)c(CCO)c2ncnn12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 28 g (0.1 mmole) of 8-(2-ethoxyethyl)-7-phenyl-1,2,4-triazolo[2,3-c]pyrimidine-5-amine (which is prepared by methods described in U.S. Pat. No. 4,405,780, the entire disclosure of which is incorporated herein by reference) was added 200 mL of 1N boron trichloride and dichloromethane. The mixture was then stirred at room temperature overnight, after which 500 mL of water was added. After three hours, the resultant precipitate was collected by filtration. The agueous phase of the filter wa separated and neutralized with agueous sodium carbonate, giving a second precipitate. The combined solids were purified by column chromatography, giving the titled compound, m.p. 194°-195°.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[S:15][C:16]=1[CH2:17][OH:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([O:40][CH3:41])[CH:33]=1.CCCCCCC.C(OC(C)C)(C)C>CN(C)C=O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=2)[S:15][C:16]=1[CH2:17][O:18][C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([O:40][CH3:41])[CH:33]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OCc1sc(-c2ccc(C(F)(F)F)cc2)nc1CCCOCc1ccccc1
Reactant: COc1cc(F)ccc1C#N
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCCC
Solvent: CC(C)OC(C)C
Solvent: CN(C)C=O
Product: COc1cc(OCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CCCOCc2ccccc2)ccc1C#N
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 71.1 %

Procedure:
To a solution of 1.34 g of [4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol in 20 mL of dimethylformamide at 0° C. was added 158 mg of a 60% suspension of sodium hydride in mineral oil. The resulting mixture was stirred for 10 minutes at 0° C. then 497 mg of 4-fluoro-2-methoxybenzonitrile were added. After stirring for 30 minutes at 0° C., the temperature was allowed to warm up to room temperature and the reaction mixture was stirred until completion. The solvent was removed under reduced pressure and dichloromethane/water were added to the residue. The organic layer was separated and the aqueous layer extracted three times with dichloromethane. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 1.82 g of crude product as a yellow oil. A 1/1 solution of heptane/diisopropyl ether was added to the residue and the solidified product was filtered off to provide a first crop of 1.26 g of desired product. The mother liquor was concentrated and purified by column chromatography on silica gel (heptane 60/ethyl acetate 40) to give an additional 110 mg. The two fractions were combined to obtain 1.37 g of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-benzonitrile.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[O:22][CH:23]=[CH:24][CH:25]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].P([O-])([O-])(O)=O.[Na+].[Na+]>CN(C)C=O.O>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:15])[F:16])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[O:22][C:23]([C:14]([F:17])([F:16])[F:15])=[CH:24][CH:25]=1
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccco1
Agent: O=P([O-])([O-])O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccc(C(F)(F)F)o1
Temperature: 45 °C
Reaction time: 16 h

Procedure:
To a solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(furan-2-yl)pyrazole (0.46 g) in dimethylformamide (15 ml) and water (5 ml) was added sodium dithionite (0.286 g) and disodium hydrogen phosphate (0.17 g). The mixture placed in a 400 ml Parr vessel, which was evacuated, then charged with trifluoromethylbromide gas to 40 psi. The mixture was shaken and heated at 45° C., for 3 hours, then left at room temperature for 16 hours. The vessel was then evacuated, then recharged with trifluoromethylbromide to 40 psi, then shaken and heated to 45° C. for a further 9 hours, then left at room temperature for 48 hours. The vessel was then evacuated, then recharged with trifluoromethylbromide to 40 psi, then shaken and heated to 45° C. for a further 7 hours, then left at room temperature for 16 hours. The mixture was filtered and then poured into brine (25 ml) and extracted with ether (25 ml, ×3). The combined organic layers were washed with water (20 ml), dried (Na2SO4), and evaporated. The residue was purified by column chromatography on silica gel (25 g) eluted with hexane:ether (50:50 changing gradually to 20:80). Combination and evaporation of suitable fractions gave the title compound as a pale yellow solid, m.p. 148-151° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][C:10]=1[C:16]1C(CCCC2C=CC=CC=2)=C(C)C=[CH:20][C:21]=1S([O-])(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:36]([NH:39][CH:40]([CH3:42])[CH3:41])([CH3:38])[CH3:37]>C(#N)C>[CH:36]([N:39]([CH2:20][CH2:21][CH:16]([C:10]1[CH:11]=[C:12]([Br:15])[CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:40]([CH3:42])[CH3:41])([CH3:38])[CH3:37]
Reactant: CC(C)NC(C)C
Reactant: Cc1ccc(S(=O)(=O)[O-])c(-c2cc(Br)ccc2OCc2ccccc2)c1CCCc1ccccc1
Solvent: CC#N
Product: CC(C)N(CCC(c1ccccc1)c1cc(Br)ccc1OCc1ccccc1)C(C)C
Yield: 163.6 %

Procedure:
3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl-p-toluenesulfonate (115 g, 0.2 mole) was dissolved in a mixture of acetonitrile (150 g) and diisopropylamine (202 g, 2.0 mole) and the mixture was refluxed for 4 days. The solution was evaporated, and to the resulting syrup was added sodium hydroxide (2M, 200 mL). The mixture was concentrated, cooled and then extracted with diethyl ether. The ethereal layer was extensively washed with water. The amine was extracted with excess sulfuric acid (1M). The aqueous layer was washed with diethyl ether and then basified with sodium hydroxide (11M). The mixture was then extracted with diethyl ether. The organic layer was washed with water, dried over sodium sulfate, filtered and then evaporated to give 78.6 g (78%) of N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropylamine as a pale yellow oil. The 1-H N.M.R spectrum was in accordance with the above structure.
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[CH2:10]1[O:19][C:18]2[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][C:12]=2[O:11]1.C(N(C(C)C)CC)(C)C.[CH3:29][CH:30]([NH2:39])[CH:31]([OH:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(#N)C>[Cl:3][C:2]1[N:1]=[C:8]([NH:15][C:14]2[CH:16]=[CH:17][C:18]3[O:19][CH2:10][O:11][C:12]=3[CH:13]=2)[N:7]=[C:5]([NH:39][C@H:30]([CH3:29])[C@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[OH:38])[N:4]=1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: Nc1ccc2c(c1)OCO2
Reactant: CC(N)C(O)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: C[C@@H](Nc1nc(Cl)nc(Nc2ccc3c(c2)OCO3)n1)[C@@H](O)c1ccccc1
Temperature: 25 °C
Yield: 80 %

Procedure:
To a solution of cyanuric chloride (1.84 gr) in acetonitrile (20 ml), kept at a temperature of −20° C. under stirring, dropwise were subsequently added solutions of 3,4-methylenedioxy-aniline (1.37 gr) in acetonitrile (20 ml) and diisopropylethylamine (DIPEA) (1.29 gr) in acetonitrile (20 ml). After stirring at −20° C. for 1 hour, again dropwise were subsequently added solutions of DIPEA (1.29 gr) in acetonitrile (20 ml) and (1 S,2R)-(+)-norephedrine (1.51 gr) in acetonitrile (20 ml). The mixture was allowed to warm to room temperature and was stirred for another 2 hours. The resulting reaction mixture was concentrated in vacuo. After addition of ethylacetate (250 ml) the organic layer was subsequently washed with a solution of HCl in water (1M, 100 ml), a solution of NaOH in water (1 M, 100 ml) and brine (50 ml). The organic layer was dried over sodiumsulphate, filtered and concentrated in vacuo. The resulting product was purified by column chromatography using silicagel and a mixture of heptane: ethylacetate (3:1) as the eluent. The resulting pure product (formula (9), see above, example B-44, see table) was obtained as a white solid in 80% yield.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][SH:4].[C:5]1([C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)O)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>FC(F)(F)C(O)=O>[C:11]([S:4][CH2:3][CH2:2][NH2:1])([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: NCCS
Reactant: OC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: NCCSC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 57.6 %

Procedure:
To a stirred solution of cysteamine (Fluka, 3.85 g, 50.0 mmol) in trifluoroacetic acid (TFA) (50 ml) was added triphenylmethanol (13.0 g, 50.0 mmol). The mixture was stirred at room temperature for 30 min and concentrated. To the residue was added ether (250 ml). Precipitated material was filtered off and washed with ether. The TFA-salt was partitioned between 1 M aqueous KOH solution (150 ml) and ether (150 ml). The phases were separated and the ether phase was dried (MgSO4). The solution was filtered and concentrated and the product was crystallised from ether/n-hexane, giving 9.20 g (58%) of white solid.
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[CH:9]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)O[C:7]2=[O:32].[N:33]1[CH:38]=[CH:37][C:36]([CH:39]=O)=[CH:35][CH:34]=1.C(N(CC)CC)C.O.[NH2:49][NH2:50]>C(Cl)Cl.O>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10]([C:9]([CH2:39][C:36]3[CH:37]=[CH:38][N:33]=[CH:34][CH:35]=3)=[N:49][NH:50][C:7]2=[O:32])=[CH:11][CH:12]=1
Reactant: COc1ccc2c(c1)C(=O)OC2[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: NN
Reactant: O=Cc1ccncc1
Agent: [Br-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: COc1ccc2c(Cc3ccncc3)n[nH]c(=O)c2c1
Temperature: 25 °C
Yield: 34.8 %

Procedure:
A solution of (5-methoxy-3-oxo-1,3-dihydro-isobenzofuran-1-yl)-triphenyl-phosphonium bromide (43,5 g, 0.0861 mole), prepared as described in example 36, and 4-pyridincarboxaldehyde (9.22 g, 0.0861 mole) in CH2Cl2 (300 ml) was dropwise added with triethylamine (12 ml, 0.0861 mole) while controlling the temperature in water bath. After 1 night under stirring at room temperature, the mixture was washed with water, discoloured, anhydrified and dried. The residue was suspended in CH3OH (135 ml) and added with hydrazine monohydrate (12.55 ml, 0.2583 mole). The mixture was refluxed for 1 hour, then cooled in water/ice, filtered and dried. The residue was crystallised in CH3OH to give 8 g of the title compound. The mother liquors were dried and the residue triturated in CH3OH (50 ml) to give further 3,5 g of the title compound (total yield: 50%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([O:9][C:10]2[C:11]([CH:21]([CH3:23])[CH3:22])=[CH:12][C:13]([O:19][CH3:20])=[C:14]([CH:16]([OH:18])[CH3:17])[CH:15]=2)=[CH:4][N:3]=1.[CH3:24]CN(S(F)(F)F)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:21]([C:11]1[CH:12]=[C:13]([O:19][CH3:20])[C:14]([CH:16]=[CH2:17])=[CH:15][C:10]=1[O:9][C:5]1[C:6]([NH2:8])=[N:7][C:2]([NH2:1])=[N:3][CH:4]=1)([CH3:23])[CH3:22].[CH:21]([C:11]1[CH:12]=[C:13]([O:19][CH3:20])[C:14]([CH:16]([O:18][CH3:24])[CH3:17])=[CH:15][C:10]=1[O:9][C:5]1[C:6]([NH2:8])=[N:7][C:2]([NH2:1])=[N:3][CH:4]=1)([CH3:23])[CH3:22]
Reactant: CCN(CC)S(F)(F)F
Reactant: COc1cc(C(C)C)c(Oc2cnc(N)nc2N)cc1C(C)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: C=Cc1cc(Oc2cnc(N)nc2N)c(C(C)C)cc1OC
Product: COc1cc(C(C)C)c(Oc2cnc(N)nc2N)cc1C(C)OC
Reaction time: 1.5 h
Yield: 3 %
Yield: 4 %

Procedure:
To a solution of 1-[5-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-ethanol (1.613 g, 5.3 mmol) in 30 ml CH2Cl2 at −78° C. was added DAST (0.935 g, 5.8 mmol). After stirring 1.5 h, saturated NaHCO3 was added and the mixture was extracted by CH2Cl2. The combined organics were washed with brine and dried Na2SO4, filtered and concentrated in vacuo. Purification via silica gel chromatography (95:5 CH2Cl2/MeOH) gave 5-(2-Isopropyl-4-methoxy-5-vinyl-phenoxy)-pyrimidine-2,4-diamine (0.044 g, 3%) as a foam ([MH]+=301) and 5-[2-Isopropyl-4-methoxy-5-(1-methoxy-ethyl)-phenoxy]-pyrimidine-2,4-diamine (0.075 g, 4%) as foam. [MH]+=303.
Reaction SMILES: [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH2:17])=[N:13][NH:14]2)=[CH:10][CH:9]=1>N1C=CC=CC=1>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH:17][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[N:13][NH:14]2)=[CH:10][CH:9]=1
Reactant: Nc1n[nH]c2cc(Cl)ccc12
Reactant: CCCC(=O)Cl
Solvent: c1ccncc1
Product: CCCC(=O)Nc1n[nH]c2cc(Cl)ccc12
Temperature: 3 °C
Reaction time: 14 h

Procedure:
0.47 cm3 of butyryl chloride is added to 750 mg of 6-chloro-1H-indazole-3-amine in 10 cm3 of pyridine, after the reaction medium has been cooled to about 3° C. The medium is then allowed to return to 19° C. over 14 hours. The reaction medium is evaporated to dryness under reduced pressure (2 kPa; 40° C.). The residue is taken up in 50 cm3 of ethyl acetate, 50 cm3 of tetrahydrofuran and 50 cm3 of distilled water. The organic phase is washed again with 50 cm3 of distilled water and with 50 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate, filtered through a sinter funnel and evaporated under reduced pressure. The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with cyclohexane/ethyl acetate (70/30 by volume) and collecting 25 cm3 fractions. The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.). After drying (90 Pa; 45° C.), 200 mg of N-(6-chloro-1H-indazol-3-yl)-butanamide are obtained in the form of a white solid melting at 230° C.