Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:9]([CH:11]([C:13]2[CH:20]=[CH:19][C:16]([O:17][CH3:18])=[CH:15][CH:14]=2)O)=O)[CH:8]=[CH:7][C:4]([O:5][CH3:6])=[CH:3][CH:2]=1.[C]=O.[H][H]>O.O.O.O.C([O-])(=O)C.[Co+2].C([O-])(=O)C.C(O)CCC>[CH3:18][O:17][C:16]1[CH:15]=[CH:14][C:13]([CH2:11][CH2:9][C:1]2[CH:2]=[CH:3][C:4]([O:5][CH3:6])=[CH:7][CH:8]=2)=[CH:20][CH:19]=1
Reactant: [H][H]
Reactant: COc1ccc(C(=O)C(O)c2ccc(OC)cc2)cc1
Agent: [Co+2]
Agent: CC(=O)[O-]
Agent: [C]=O
Solvent: O
Solvent: CCCCO
Product: COc1ccc(CCc2ccc(OC)cc2)cc1
Temperature: 200 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
The autoclave described in EXAMPLE 1 was employed. To this autoclave was charged 11.0 grams (0.040 mole) of anisoin, 2.0 grams (0.0080 mole) of cobalt(II) acetate tetrahydrate, and 70 milliliters of 1-butanol. The autoclave was thereafter charged to 1100 psig with carbon monoxide and heated, with stirring at 800 rpm, to 200° C. Hydrogen was then charged to the autoclave to a total pressure of 3800 psig for a hydrogen to carbon monoxide molar ratio of 2:1. The reaction was allowed to continue for a period of 1 hour, and thereafter cooled to about 70° C. Gas chromatographic analysis of the homogeneous product solution indicated a 90 percent yield of 1,2-bis(4-methoxyphenyl)ethane.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH3:13])[C:9]([OH:11])=[N:10][C:5]2=[N:4][CH:3]=1.C(N(CC)CC)C.C([Sn](CCCC)(CCCC)[C:32]([O:34]CC)=[CH2:33])CCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[OH:11][C:9]1[N:8]([C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[C:6]2=[N:7][C:2]([C:32](=[O:34])[CH3:33])=[CH:3][N:4]=[C:5]2[N:10]=1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: C[C@@H](c1ccccc1)n1c(O)nc2ncc(Br)nc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(=O)c1cnc2nc(O)n([C@@H](C)c3ccccc3)c2n1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 33 %

Procedure:
An oven-dried scintillation vial equipped with a stirbar was charged with (S)-6-bromo-1-(1-phenylethyl)-1H-imidazo[4,5-b]pyrazin-2-ol (1.0 equiv), and (Ph3P)4Pd (0.07 equiv). The bottle was covered with a sheet of Parafilm and purged with nitrogen for 5 min, and anhydrous dioxane (13 volume equivalents), triethylamine (3.0 equiv), and tributyl(1-ethoxyvinyl)stannane (1.5 equiv) were added by syringe. The resulting mixture was heated to 80° C. overnight. The reaction was quenched with 1 N KHSO4 and stirred for 30 min. The mixture was then diluted with EtOAc, washed twice with NaHCO3 and once with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Biotage MPLC 10%-66% EtOAc/Hexanes) provided the title compound (33%) as a white solid. LCMS m/z (APCI)=283.1 (M+H).
Reaction SMILES: CN(C)C=O.CS(O[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:18])[F:17])(=O)=O.O.O.[CH3:22][N:23]([CH3:27])[C:24](=[S:26])[S-:25].[Na+]>O>[CH3:22][N:23]([CH3:27])[C:24](=[S:25])[S:26][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:17])[F:18]
Reactant: CN(C)C(=S)[S-]
Reactant: CC(CCCCOS(C)(=O)=O)=C(F)F
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(CCCCSC(=S)N(C)C)=C(F)F
Temperature: 100 °C
Reaction time: 3 h
Yield: 51.3 %

Procedure:
To 100 ml of N,N-dimethylformamide, 4.56 g (20 mmol) of 6,6-difluoro-5-methyl-5-hexenyl methanesulfonate and 4.70 g (26 mmol) of sodium dimethyldithiocarbamate dihydrate were dissolved, followed by stirring at 100° C. for 3 hours. The reaction liquid was poured into water and extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10) to obtain 2.60 g (yield: 51%) of 6,6-difluoro-5-methyl-5-hexenyl N,N-dimethyldithiocarbamate.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][C:18]#[N:19])[CH:12]=1.C([O-])([O-])=O.[K+].[K+]>C(O)=C>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17](=[CH:4][C:3]2[CH:6]=[CH:7][C:8]([Cl:10])=[CH:9][C:2]=2[Cl:1])[C:18]#[N:19])[CH:12]=1
Reactant: O=Cc1ccc(Cl)cc1Cl
Reactant: N#CCc1cccnc1
Agent: C=CO
Agent: O=C([O-])[O-]
Agent: [K+]
Product: N#CC(=Cc1ccc(Cl)cc1Cl)c1cccnc1
Reaction time: 0.25 h
Yield: 75.2 %

Procedure:
To a stirred solution of 2,4-dichlorobenzaldehyde (5.0 g, 29 mmole) and 3-pyridylacetonitrile (3.05 ml, 29 mmole) in 150 ml absolute ethenol were added 3.95 K2CO3. After stirring for about 15 minutes, a white solid precipitated out of the reaction mixture. The reaction mixture was stirred overnight and filtered. The filter cake was washed with absolute ethanol and dissolved in CH2Cl2. The CH2Cl2 solution was filtered and concentrated in vacuo. The resulting white solid was recrystallized from 3:2 hexane/ethyl acetate to give 6.0 g (76%) of the title compound.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([C:20]#[N:21])([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:6]([O:8][CH3:9])=[O:7].[CH3:22][NH:23][CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=1)[C:29]([O:31][CH3:32])=[O:30]>>[C:20]([C:5]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)([C:6]([O:8][CH3:9])=[O:7])[CH2:4][CH2:3][CH2:2][N:23]([CH3:22])[CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=1)[C:29]([O:31][CH3:32])=[O:30])#[N:21]
Reactant: COC(=O)C(C#N)(CCCBr)c1ccc(OC)c(OC)c1
Reactant: CNCCc1cccc(C(=O)OC)c1
Product: COC(=O)c1cccc(CCN(C)CCCC(C#N)(C(=O)OC)c2ccc(OC)c(OC)c2)c1

Procedure:
Reaction of 1b with 2d produced 3t. MS found M+H=469. The oxalate salt of 3t was recrystallized from ethyl acetate; mp 94-95° C.
Reaction SMILES: ClC1N=NC(N(C)[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:11]=2)=C(C2C=CC(F)=CC=2OC)C=1.S(Cl)([Cl:37])=O>CN(C)C=O>[CH3:23][S:20]([C:12]1[CH:11]=[C:10]([CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=1)[C:9]([Cl:37])=[O:24])(=[O:22])=[O:21]
Reactant: O=S(Cl)Cl
Reactant: COc1cc(F)ccc1-c1cc(Cl)nnc1N(C)C(=O)c1cc(C(F)(F)F)cc(S(C)(=O)=O)c1
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1cc(C(=O)Cl)cc(C(F)(F)F)c1
Yield: 102.9 %

Procedure:
To 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (1 g, 3.73 mmol, example 1, intermediate d) was added N,N-dimethylformamide (27.3 mg, 28.9 μL, 373 μmol) and thionyl chloride (8.87 g, 5.44 ml, 74.5 mmol) and the suspension was heated to reflux for 30 min. A light brown solution was formed. To remove thionyl chloride, the light brown solid was diluted with toluene, followed by complete evaporation. This procedure was repeated two times to provide the desired compound as a colorless solid (1.1 g; 99%) which was pure enough for the next step without further purification.
Reaction SMILES: [Li+].[OH-].[CH3:3][C:4]([CH3:27])([CH2:24][CH:25]=[CH2:26])[CH2:5][N:6]([CH3:23])[C:7]([NH:9][C@@H:10]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[CH2:22])[C:11]([O:13]CC)=[O:12])=[O:8]>CO.O.C1COCC1>[CH3:3][C:4]([CH3:27])([CH2:24][CH:25]=[CH2:26])[CH2:5][N:6]([CH3:23])[C:7]([NH:9][C@@H:10]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[CH2:22])[C:11]([OH:13])=[O:12])=[O:8]
Reactant: C=CCCCCC[C@H](NC(=O)N(C)CC(C)(C)CC=C)C(=O)OCC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: C=CCCCCC[C@H](NC(=O)N(C)CC(C)(C)CC=C)C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
LiOH (66 mmol) was added to a solution of ethyl (2S)-2-({[(2,2-dimethylpent-4-en-1-yl)(methyl)amino]carbonyl}amino)non-8-enoate (2.35 g, 6.67 mmol) in MeOH (20 mL), water (10 mL) and THF (30 mL). The reaction mixture was stirred for 3 hours at RT and then concentrated. A solution 5% potassium bisulfate was added, and the mixture was extracted with EtOAc (3×). The combined organic were washed with brine, dried over MgSO4, filtered and concentrated to give the title compound. LRMS (M+H)+=325.3.
Reaction SMILES: [C:1]([C:5]1[O:9][C:8]([C:10]([O:12]CC)=O)=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:15]1([C@@H:21]([NH2:23])[CH3:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[C:15]1([C@@H:21]([NH:23][C:10]([C:8]2[O:9][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[N:6][N:7]=2)=[O:12])[CH3:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CCOC(=O)c1nnc(C(C)(C)C)o1
Reactant: C[C@H](N)c1ccccc1
Solvent: CCO
Product: C[C@H](NC(=O)c1nnc(C(C)(C)C)o1)c1ccccc1
Yield: 92 %

Procedure:
A solution of ethyl 5-tert-butyl-[1,3,4]oxadiazole-2-carboxylate (1.38 g, 7 mmol) and (S)-1-phenylethylamine (1.70 g, 14 mmol) in absolute ethanol (25 ml) is refluxed for 6 hours. The solvent is evaporated in vacuo and the residue is purified by flash column chromatography (silica gel, hexane/ethyl acetate 4:1 v/v) to give (S)-5-tert-butyl-[1,3,4]oxadiazole-2-carboxylic acid (1-phenylethyl)amide (1.76 g, 92%) as colourless crystals, m.p. 123°-125° C.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:8]2[CH2:7][CH:6]([CH2:11][N:12]3[C:17]4=[N:18][C:19]([C:23]5[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=5)=[CH:20][C:21](=[O:22])[N:16]4[CH2:15][C:14]([CH3:30])([CH3:29])[CH2:13]3)[CH2:5][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[N:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1.O>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:29][C:14]1([CH3:30])[CH2:15][N:16]2[C:21](=[O:22])[CH:20]=[C:19]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[N:18]=[C:17]2[N:12]([CH2:11][CH:6]2[CH2:5][C:4]3[N:3]=[C:2]([C:40]4[CH:41]=[CH:42][N:37]=[CH:38][CH:39]=4)[CH:10]=[CH:9][C:8]=3[CH2:7]2)[CH2:13]1
Reactant: OB(O)c1ccncc1
Reactant: CC1(C)CN(CC2Cc3ccc(Cl)nc3C2)c2nc(-c3ccncc3)cc(=O)n2C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: CC1(C)CN(CC2Cc3ccc(-c4ccncc4)nc3C2)c2nc(-c3ccncc3)cc(=O)n2C1
Temperature: 140 °C
Reaction time: 24 h
Yield: 20.2 %

Procedure:
To a solution of 0.22 g (0.521 mmol) of (+/−)9-(2-chloro-6,7-dihydro-5H-[1]pyrindin-6-ylmethyl)-7,7-dimethyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one in 3 ml of anhydrous toluene and 0.5 ml of ethanol was treated with 0.625 ml (2M solution in water) of sodium carbonate, 36 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium and 0.096 g (0.781 mmol) of pyridine-4-boronic acid. After being stirred for 24 h at 140° C., water was added, the mixture was extracted with dichloromethane. The organic phase was dried and evaporated to give crude product, which was purified by silica gel chromatography, eluting with dichloromethane/methanol/ammonia in the proportions 99/1/0.1 to give 0.049 g of pure product obtained in the form of free base. Mp: 170-171° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12](=[O:52])[C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH2:31][CH2:30][C:29]([CH3:33])([CH3:32])[CH2:28][C:27]=4[C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=4)[CH2:21][CH2:20]3)=[CH:15][C:14]=2[O:41][C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][C:50]=2[F:51])[NH:47][CH:46]=[CH:45]3)(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:53]([O-:55])=[O:54].[NH2:56][CH2:57][C@H:58]1[CH2:63][CH2:62][C@H:61]([OH:64])[CH2:60][CH2:59]1.C(N(C(C)C)C(C)C)C>O1CCOCC1>[Cl:40][C:37]1[CH:36]=[CH:35][C:34]([C:27]2[CH2:28][C:29]([CH3:32])([CH3:33])[CH2:30][CH2:31][C:26]=2[CH2:25][N:22]2[CH2:21][CH2:20][N:19]([C:16]3[CH:17]=[CH:18][C:13]([C:12]([NH:11][S:8]([C:5]4[CH:6]=[CH:7][C:2]([NH:56][CH2:57][C@H:58]5[CH2:63][CH2:62][C@H:61]([OH:64])[CH2:60][CH2:59]5)=[C:3]([N+:53]([O-:55])=[O:54])[CH:4]=4)(=[O:10])=[O:9])=[O:52])=[C:14]([O:41][C:42]4[CH:43]=[C:44]5[C:48](=[CH:49][C:50]=4[F:51])[NH:47][CH:46]=[CH:45]5)[CH:15]=3)[CH2:24][CH2:23]2)=[CH:39][CH:38]=1
Reactant: CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(Cl)c([N+](=O)[O-])c4)c(Oc4cc5cc[nH]c5cc4F)c3)CC2)=C(c2ccc(Cl)cc2)C1
Reactant: NC[C@H]1CC[C@H](O)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@H]5CC[C@H](O)CC5)c([N+](=O)[O-])c4)c(Oc4cc5cc[nH]c5cc4F)c3)CC2)=C(c2ccc(Cl)cc2)C1

Procedure:
A mixture of EXAMPLE 240A (153 mg), trans-4-(aminomethyl)cyclohexanol (73.5 mg) and N-ethyl-N-isopropylpropan-2-amine (0.16 mL) in dioxane (2 mL) was heated at 100° C. for 20 hours and concentrated. The residue was dissolved in dimethylsulfoxide-methanol (1:1) and purified by HPLC, eluting with 40%-65% acetonitrile in 0.1% TFA water over 40 minutes to provide the title compound. 1H NMR (500 MHz, dimethylsulfoxide-d6) δ 11.22 (s, 2H), 8.56-8.62 (m, 2H), 7.85 (dd, 1H), 7.51 (d, 1H), 7.38 (t, 1H), 7.29-7.36 (m, 4H), 7.12 (d, 1H), 7.03 (d, 2H), 6.66 (dd, 1H), 6.41 (s, 1H), 6.09 (d, 1H), 4.51 (d, 1H), 3.24 (t, 2H), 3.03 (s, 4H), 2.74 (s, 2H), 2.16 (d, 6H), 1.95 (s, 2H), 1.83 (d, 2H), 1.74 (d, 2H), 1.56 (dd, 1H), 1.38 (t, 2H), 0.95-1.16 (m, 4H), 0.92 (s, 6H).
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:14](OC(=O)C)(=[O:16])[CH3:15].[Cl-].[Al+3].[Cl-].[Cl-]>>[C:14]([C:9]1[CH:8]=[CH:7][C:6]2[C:5]3[C:13](=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH2:12][C:11]=2[CH:10]=1)(=[O:16])[CH3:15]
Reactant: CC(=O)OC(C)=O
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Agent: [Al+3]
Agent: [Cl-]
Product: CC(=O)c1ccc2c(c1)Cc1ccccc1-2

Procedure:
Known in the present-day practice is a method of producing the bisulfite compound of 2-fluorenonyl-glyoxal, said method consisting in that fluorene is acylated by acetic anhydride in the presence of aluminum chloride to obtain 2-acetylfluorene at a yield of 60 weight percent. Then the thus-obtained 2-acetylfluorene is oxidized by sodium bichromate in an acetic-acid medium at 70°-75° C during 6 hours and 2-acetylfluorenon is isolated at a yield of 50 weight percent.
Reaction SMILES: [CH3:1][C:2]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:3]=1[CH:4]=[C:5]1[C:17]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]2=3)[CH:7]=[CH:6]1.[OH2:18].[OH2:19].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:21].[Na+].[Na+]>C(O)(=O)C>[CH3:1][C:2]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:3]=1[CH:4]=[C:5]1[C:6]([O:19][C:7](=[O:21])[C:8]3[C:17]1=[C:12]2[CH:11]=[CH:10][CH:9]=3)=[O:18]
Reactant: Cc1cccc2c1cc1c3c(cccc32)C=C1
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Reactant: O
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1cccc2c1cc1c3c(cccc32)C(=O)OC1=O
Yield: 82.4 %

Procedure:
A suspension of 7-methylacephenanthrylene (0.56 g, 2.59 mmol) and sodium dichromate dihydrate (2.70 g, 9.07 mmol) in glacial acetic acid (10 mL) was heated at reflux for 4 h. The reaction mixture was allowed to cool and the resulting solid was collected by suction filtration. The solid was dried to give 0.56 g (80%) of the anhydride: MS (CI) m/e (%) 263 (M+H+, 100); 1H NMR (DMSO-d6, 300 MHz) δ 9.55 (d, 1H, J=8.8 Hz), 9.04 (s, 1H), 8.89 (d, 1H, J=8.5 Hz), 8.55 (d, 1H, J=7.4 Hz), 7.75 (d, 1H, J=7.3 Hz), 2.87 (s, 3H).
Reaction SMILES: [CH2:1]([N:3]([CH2:7][CH3:8])[CH2:4][CH2:5][Cl:6])[CH3:2].[K].[CH3:10][O:11][C:12]1[CH:13]=[C:14]2[O:18][CH:17]([CH3:19])[CH2:16][C:15]2=[C:20]([NH2:22])[CH:21]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[ClH:6].[ClH:6].[CH2:1]([N:3]([CH2:7][CH3:8])[CH2:4][CH2:5][NH:22][C:20]1[C:15]2[CH2:16][CH:17]([CH3:19])[O:18][C:14]=2[CH:13]=[C:12]([O:11][CH3:10])[CH:21]=1)[CH3:2]
Reactant: CCN(CC)CCCl
Reactant: COc1cc(N)c2c(c1)OC(C)C2
Agent: [K]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CCN(CC)CCNc1cc(OC)cc2c1CC(C)O2
Product: Cl
Yield: 97.9 %

Procedure:
2.80 grams of 2-diethylamino-ethyl chloride and traces of potassium jodide are added to a solution of 3 grams of 2,3-dihydro-6-methoxy-2-methyl-4-benzofuranamine and 2.02 grams of triethylamine in 50 cc of anhydrous toluene and the resulting reaction mixture is refluxed for 16 hours. After cooling and washing with water, the toluene phase is dried over Na2SO4 and then concentrated to dryness. Hydrochloric acid is added to an ether solution of the resulting oily residue until a solid precipitates then the mixture is cooled. The precipitate is recovered on filter and recrystallized from ethanol by addition of ethyl ether, yielding 3.55 grams of the title compound. M.p. 158°-159° C.
Reaction SMILES: [S:1]1[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2.[Cl:13][CH2:14][C:15]([CH2:17]Cl)=O>>[S:1]1[C:5]([C:6]2[O:7][CH:17]=[C:15]([CH2:14][Cl:13])[N:8]=2)=[CH:4][C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2
Reactant: NC(=O)c1cc2ccccc2s1
Reactant: O=C(CCl)CCl
Product: ClCc1coc(-c2cc3ccccc3s2)n1
Yield: 33 %

Procedure:
In substantially the same manner as in Reference Example 31, 2-benzo[b]thiophenecarboxamide was allowed to react with 1,3-dichloroacetone to give 2-(2-benzo[b]thienyl)-4-chloromethyloxazole. The yield was 33%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 150-151° C.
Reaction SMILES: [F:1][CH:2]([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[OH:26][CH2:27][CH2:28][N:29]([CH3:40])[S:30]([C:33]1[S:37][C:36]([NH2:38])=[N:35][C:34]=1[CH3:39])(=[O:32])=[O:31]>>[OH:26][CH2:27][CH2:28][N:29]([CH3:40])[S:30]([C:33]1[S:37][C:36]([NH:38][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([CH:2]([F:25])[F:1])=[CH:4][C:5]([C:15]4[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=4)=[N:6][C:7]=23)=[O:13])=[N:35][C:34]=1[CH3:39])(=[O:31])=[O:32]
Reactant: O=C(O)c1cnn2c(C(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: Cc1nc(N)sc1S(=O)(=O)N(C)CCO
Product: Cc1nc(NC(=O)c2cnn3c(C(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)sc1S(=O)(=O)N(C)CCO

Procedure:
The title compound was prepared from 7-difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C. 1) and 2-amino-4-methyl-thiazole-5-sulfonic acid (2-hydroxy-ethyl)-methyl-amide (example B.20) according to general procedure II.
Reaction SMILES: [C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.Cl.Cl.[F:38][C:39]([F:62])([F:61])[C:40]1[CH:41]=[C:42]([N:46]2[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][C@@H:54]3[CH2:59][CH2:58][C@H:57]([NH2:60])[CH2:56][CH2:55]3)[CH2:48][CH2:47]2)[CH:43]=[CH:44][CH:45]=1>ClCCl>[C:1]([CH2:3][C:4]([NH:60][CH:57]1[CH2:58][CH2:59][CH:54]([CH2:53][CH2:52][N:49]2[CH2:48][CH2:47][N:46]([C:42]3[CH:43]=[CH:44][CH:45]=[C:40]([C:39]([F:62])([F:61])[F:38])[CH:41]=3)[CH2:51][CH2:50]2)[CH2:55][CH2:56]1)=[O:6])#[N:2]
Reactant: N[C@H]1CC[C@@H](CCN2CCN(c3cccc(C(F)(F)F)c3)CC2)CC1
Reactant: N#CCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: N#CCC(=O)NC1CCC(CCN2CCN(c3cccc(C(F)(F)F)c3)CC2)CC1
Reaction time: 0.25 h

Procedure:
To a solution of 43 mg (0.5 mmol) of cyanoacetic acid in 5 mL of dichloromethane stabilized on amylene are successively added 68 mg (0.5 mmol) of 1-hydroxybenzotriazole, 96 mg (0.5 mmol) of 3-ethyl-1-(3-dimethylaminopropyl)-carbodiimide hydrochloride and 0.21 mL (1.5 mmol) of triethylamine. The mixture is stirred for 15 minutes then 214 mg (0.5 mmol) of the 80%/20% trans/cis 4-{2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethyl}cyclohexylamine dihydrochloride is added. The mixture is stirred overnight at room temperature.
Reaction SMILES: COC(OC)[N:4]([CH3:6])[CH3:5].O[CH:10]=[CH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[O:13].C(N)=[NH:22].C[O-].[Na+]>C1(C)C=CC=CC=1.C(O)C.O>[N:4]1[CH:5]=[C:11]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[O:13])[CH:10]=[N:22][CH:6]=1
Reactant: O=C(C=CO)c1ccc(Cl)cc1
Reactant: COC(OC)N(C)C
Reactant: N=CN
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=C(c1ccc(Cl)cc1)c1cncnc1
Reaction time: 0.25 h
Yield: 30.8 %

Procedure:
7.7 g (0.065 mole) of N,N-dimethylformamide dimethyl acetal are added in portions to 10 g (0.055 mole) of 4-chlorophenyl hydroxyvinyl ketone (compare 1st stage) in 10 ml of toluene at 0° C. The reaction mixture is subsequently stirred for 15 minutes, and 5.7 g (0.055 mole) of formamidine kacetate are then added. After further subsequent stirring for 15 minutes, a solution of 3 g (0.055 mole) of sodium methylate in 80 ml of ethanol is added dropwise and the mixture is subsequently stirred under reflux for 8 hours. The reaction mixture is allowed to cool and is poured onto 400 ml of water and extracted with toluene. The organic phase is washed with water, dried over sodium sulphate and concentrated. The residue is purified by column chromatography (ethyl acetate: cyclohexane=3:1; silica gel). 3.7 g (31% of theory) of 4-chlorophenyl 5-pyrimidinyl ketone of melting point 110°-112° C. are obtained.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([OH:18])[CH:8]=[CH:9][C:10]=1[O:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:21]([O:23][CH:24]([O:27][CH2:28][CH3:29])[CH2:25]Br)[CH3:22]>CN(C)C=O>[C:1]([C:5]1[CH:6]=[C:7]([O:18][CH2:25][CH:24]([O:27][CH2:28][CH3:29])[O:23][CH2:21][CH3:22])[CH:8]=[CH:9][C:10]=1[O:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(CBr)OCC
Reactant: CC(C)(C)C(=O)Oc1ccc(O)cc1C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(COc1ccc(OC(=O)C(C)(C)C)c(C(C)(C)C)c1)OCC
Reaction time: 0.5 h
Yield: 21 %

Procedure:
0.70 g of 3-t-butyl-4-trimethylacetoxyphenol was dissolved in 7 ml of dimethylformamide and the solution was added dropwise into a suspension of 0.13 g of oily sodium hydride in 7 ml of dimethylformamide at 0° C. under a nitrogen stream. After stirring for 30 minutes, 0.50 ml of bromoacetaldehyde diethylacetal was added dropwise and the solution was stirred overnight and allowed to attain room temperature. After the reaction was quenched with a saturated aqueous ammonium chloride solution, the reaction mixture was extracted with water and ethyl acetate and the organic layers were washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated. The concentrate was purified by silica gel column chromatography (in n-hexane containing 1%-5% ethyl acetate) to give 0.21 g of 3-t-butyl-1-(2,2-diethoxyethoxy)-4-trimethylacetoxybenzene as a white solid (yield 21%).
Reaction SMILES: [N+](C1C=C([N+]([O-])=O)C=CC=1[O-])([O-])=O.[NH2:14][N+:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Br:21])[CH:16]=1.[CH3:22][O:23][C:24](=[O:31])[C:25]#[C:26][C:27]([CH3:30])([CH3:29])[CH3:28].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:22][O:23][C:24]([C:25]1[C:26]([C:27]([CH3:30])([CH3:29])[CH3:28])=[N:14][N:15]2[CH:16]=[C:17]([Br:21])[CH:18]=[CH:19][C:20]=12)=[O:31]
Reactant: N[n+]1cccc(Br)c1
Reactant: COC(=O)C#CC(C)(C)C
Agent: O=C([O-])[O-]
Agent: O=[N+]([O-])c1ccc([O-])c([N+](=O)[O-])c1
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1c(C(C)(C)C)nn2cc(Br)ccc12
Temperature: 25 °C
Yield: 23.6 %

Procedure:
To a solution of 1-amino-3-bromo-pyridinium 2,4-dinitro-phenolate (example 41, step 1) (1.98 g, 14.16 mmol) in DMF (20 ml) were added 4,4-dimethyl-pent-2-ynoic acid methyl ester (CAS 20607-85-6) (5 g, 14.16 mmol, 1 equiv.) and K2CO3 (3.9 g, 28.3 mmol, 2 equiv.) and stirred at 25° C. while purging air. DMF was completely evaporated, the residue dissolved in ethyl acetate and washed with water (100 ml). The organic extract was dried with sodium sulfate, filtered and evaporated to dryness. The resulting crude product along with the undesired regioisomer 4-bromo-2-tert-butyl-pyrazolo[1,5-a]pyridine-3-carboxylic acid methyl ester was purified by column chromatography. The desired 6-bromo-2-tert-butyl-pyrazolo[1,5-a]pyridine-3-carboxylic acid methyl ester (1.04 g, 24% yield) was obtained as a white solid, MS: m/e=312.2 (M+H+).