Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:8][C:9]2[N:14]3[N:15]=[C:16]([NH2:18])[N:17]=[C:13]3[CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[CH:1]1([NH:8][C:9]2[N:14]3[N:15]=[C:16]([NH:18][C:25](=[O:26])[C:24]4[CH:28]=[CH:29][C:21]([CH2:20][N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)=[CH:22][CH:23]=4)[N:17]=[C:13]3[CH:12]=[CH:11][CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: Nc1nc2cccc(NC3CCCCCC3)n2n1
Reactant: C1COCCN1
Reactant: O=C(Cl)c1ccc(CCl)cc1
Product: O=C(Nc1nc2cccc(NC3CCCCCC3)n2n1)c1ccc(CN2CCOCC2)cc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 40.1 %

Procedure:
The title compound was prepared following procedure described for intermediate B1, but starting from N5-cycloheptyl[1,2,4]triazolo[1,5-a]pyridine-2,5-diamine ((A10), 123 mg; 0.50 mmol; 1.0 eq.) and 4-(chloromethyl)benzoyl chloride (142 mg; 0.75 mmol; 1.5 eq.). Solvents were removed under reduced pressure to yield a gummy solid that was resuspended in morpholine (1.74 g; 20.0 mmol; 10.0 eq.) and the mixture was stirred at 60° C. for 2 h. After this time, reaction mixture was cooled down to rt, solvents were evaporated under reduced pressure and the residue washed with Et2O (4×5 mL). A solid crystallized in the Et2O phase which, after filtration, gave the title compound as a white solid (90 mg, 40%). HPLC, Rt: 3.99 min. (purity 98.9%). LC/MS, M+(ESI): 423.1, M−(ESI): 421.1.
Reaction SMILES: C(O[C:4](=O)[CH2:5][C:6](=O)[C:7]1C=CC=C[C:8]=1N=NC1C=CC(Cl)=CC=1)C.Cl[C:25]1[CH:30]=[CH:29][C:28]([N:31]2[N:35]=[C:34]([CH:36]=[O:37])[C:33]([CH3:38])=[N:32]2)=[CH:27][CH:26]=1.C(OC(=O)C(N=NC1C=CC(Cl)=CC=1)C(C)=O)C>>[CH:36]([C:34]1[C:33]([C:38]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:32][N:31]([C:28]2[CH:29]=[CH:30][CH:25]=[CH:26][CH:27]=2)[N:35]=1)=[O:37]
Reactant: CCOC(=O)CC(=O)c1ccccc1N=Nc1ccc(Cl)cc1
Reactant: Cc1nn(-c2ccc(Cl)cc2)nc1C=O
Agent: CCOC(=O)C(N=Nc1ccc(Cl)cc1)C(C)=O
Product: O=Cc1nn(-c2ccccc2)nc1-c1ccccc1

Procedure:
In a similar manner, 2-(4'-chlorophenyl)-4-formyl-5-phenyl-1,2,3-triazole of melting point 137° - 138° C. is obtained using 2-(4'-chlorophenylazo)-benzoylacetic acid ethyl ester and 2-(4'chlorophenyl)-4-formyl-5-methyl-1,2,3-triazole of melting point 110° - 111° C. is obtained using 2-(4'-chlorophenylazo)-acetoacetic acid ethyl ester.
Reaction SMILES: C(OC([N:8]1[C:12]2=[C:13]([Cl:26])[N:14]=[CH:15][C:16]([C:17](=[O:25])[NH:18][CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[C:11]2[C:10]([CH3:27])=[CH:9]1)=O)(C)(C)C.CS(O)(=O)=O.[CH:33]1([NH2:39])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>C(OCC)(=O)C>[ClH:26].[O:22]1[CH2:21][CH2:20][CH:19]([NH:18][C:17]([C:16]2[C:11]3[C:10]([CH3:27])=[CH:9][NH:8][C:12]=3[C:13]([NH:39][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[N:14][CH:15]=2)=[O:25])[CH2:24][CH2:23]1
Reactant: NC1CCCCC1
Reactant: Cc1cn(C(=O)OC(C)(C)C)c2c(Cl)ncc(C(=O)NC3CCOCC3)c12
Agent: CS(=O)(=O)O
Solvent: CCOC(C)=O
Product: Cc1c[nH]c2c(NC3CCCCC3)ncc(C(=O)NC3CCOCC3)c12
Product: Cl
Reaction time: 15 h

Procedure:
Prepared in a similar manner to Example 12, from 7-chloro-3-methyl-4-(tetrahydro-pyran-4-ylcarbamoyl)-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester except that the methanesulfonic acid was omitted. Cyclohexylamine (900 ul) was used and the reaction time was 15 h. Ethyl acetate was used instead of dichloromethane as solvent in the work up, no chromatography was required, and ethyl acetate was used instead of dichloromethane in the salt formation, to give the title compound (13 mg).
Reaction SMILES: [CH2:1]([O-:4])[CH:2]=[CH2:3].[Na+].[Na].[CH3:7][S:8][C:9]1[N:14]=[C:13]([NH:15][CH:16]([CH3:18])[CH3:17])[C:12]([N+:19]([O-:21])=[O:20])=[C:11](Cl)[N:10]=1>C(O)C=C>[CH3:7][S:8][C:9]1[N:14]=[C:13]([NH:15][CH:16]([CH3:18])[CH3:17])[C:12]([N+:19]([O-:21])=[O:20])=[C:11]([O:4][CH2:1][CH:2]=[CH2:3])[N:10]=1
Reactant: CSc1nc(Cl)c([N+](=O)[O-])c(NC(C)C)n1
Reactant: C=CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: C=CCO
Product: C=CCOc1nc(SC)nc(NC(C)C)c1[N+](=O)[O-]
Temperature: 20 °C
Reaction time: 8 h

Procedure:
A solution of sodium allyl alcoholate (prepared from 1.2 g (50 m-moles of sodium in 50 ml of allyl alcohol) is added to 13.2 g (50 m-moles) of 2-methylthio-4-isopropylamino-5-nitro-6-chloro-pyrimidine and the mixture is stirred overnight at 20° C. The allyl alcohol is evaporated off, the residue is suspended in water and extracted with ether. The ethereal extracts are dried over MgSO4 and concentrated to yield 15 g of 2-methylthio-4-isopropylamino-5-nitro-6-allyloxypyrimidine of m.p. 51°-54° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]([N:26]3[CH2:30][CH2:29][S:28][CH2:27]3)=[O:25])[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.ClC1C=C(C2N(C3C=NC=CC=3)N=C(C(N3CCS(=O)C3)=[O:51])C=2)C=C(F)C=1.ClC1C=CC=C(C(OO)=O)C=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]([N:26]3[CH2:30][CH2:29][S:28](=[O:51])[CH2:27]3)=[O:25])[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:10])([F:11])[F:12])[CH:7]=1
Reactant: O=C(c1cc(-c2cc(Cl)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1)N1CCSC1
Reactant: O=C(c1cc(-c2cc(F)cc(Cl)c2)n(-c2cccnc2)n1)N1CCS(=O)C1
Agent: O=C(OO)c1cccc(Cl)c1
Product: O=C(c1cc(-c2cc(Cl)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1)N1CCS(=O)C1

Procedure:
38 mg (0.08 mmol) of the compound of Example 77 is reacted analogously to the synthesis of the compound of Example 6 with 21 mg (0.08 mmol, 70%) of meta-chloroperbenzoic acid for 4 hours at room temperature. 39 mg (99% of theory) of the title compound is obtained.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].C[CH2:11][CH:12]([OH:17])[C:13](OC)=O.CCC(O)C(OC)=O.N[C@H](C(O)=O)CC(C)C.C(OC(=O)[C@H](CC(C)C)N)C.N[C@H](C(O)=O)C[CH2:49][S:50]C.CCC(O)C(OC)=O.N[C@H](C(O)=O)CCSC>>[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH2:4][S:50][CH3:49].[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][C:4]1[CH:6]=[CH:13][C:12]([OH:17])=[CH:11][CH:5]=1
Reactant: CC(C)C[C@H](N)C(=O)O
Reactant: CCC(O)C(=O)OC
Agent: CCOC(=O)[C@@H](N)CC(C)C
Agent: CSCC[C@H](N)C(=O)O
Product: N[C@@H](Cc1ccc(O)cc1)C(=O)O

Procedure:
The papain-catalyzed synthesis of leucine and MHBA co-oligomers was also explored. Synthesis of leucine oligomers and MHBA-leucine co-oligomers was initiated with leucine ethyl ester and MHBA ethyl ester as the substrates. The overall synthesis and purification approach was similar to the one used in the case of methionine and MHBA-methionine. Reaction rates similar to those obtained with methionine and tyrosine were achieved. Approximate oligomer yield was 58%. The freeze-dried oligomers precipitates were solubilized in DMSO. The solution concentration was brought to approximately 2 μg/μl. The solution was mixed with 1:1 acetonitrile:water mixture containing 0.1% acetic acid. The total fluid volume entering the ESI-MS was maintained at 0.2 mL min.−1 The positive mass spectrum of the leucine oligomers is shown in FIG. 33A.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[C:6](=[O:18])[C:5]=2[NH:4][N:3]=1.[C:19](=[O:22])([O-])[O-].[K+].[K+].[CH3:25][O:26][C:27]1[C:44]([O:45][CH3:46])=[C:43]([O:47][CH3:48])[CH:42]=[CH:41][C:28]=1[CH2:29][N:30]1[CH2:35][CH2:34][N:33]([C:36](=O)[CH2:37]CCl)[CH2:32][CH2:31]1>>[NH2:1][C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[C:6](=[O:18])[C:5]=2[N:4]([C:19](=[O:22])[CH2:37][CH2:36][N:33]2[CH2:34][CH2:35][N:30]([CH2:29][C:28]3[CH:41]=[CH:42][C:43]([O:47][CH3:48])=[C:44]([O:45][CH3:46])[C:27]=3[O:26][CH3:25])[CH2:31][CH2:32]2)[N:3]=1
Reactant: Cc1ccc(N2CCc3c(N)n[nH]c3C2=O)cc1
Reactant: O=C([O-])[O-]
Reactant: COc1ccc(CN2CCN(C(=O)CCCl)CC2)c(OC)c1OC
Agent: [K+]
Product: COc1ccc(CN2CCN(CCC(=O)n3nc(N)c4c3C(=O)N(c3ccc(C)cc3)CC4)CC2)c(OC)c1OC

Procedure:
A target compound (158.4 mg, 0.281 mmol, 53.8%) was yielded as white solid in the same manner as Example 1 by reacting 3-amino-5,6-dihydro-6-N-(p-tolyl)-1H-pyrazolo[3,4-c]pyridin-7(4H)-one (126.8 mg, 0.523 mmol) with potassium carbonate (108.3 mg, 0.784 mmol) and 1-{4-(2,3,4-trimethoxybenzyl)piperazin-1-yl}-3-chloropropan-1-one (205.1 mg, 0.575 mmol).
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([S:12](Cl)(=[O:14])=[O:13])[CH2:8][CH2:7]2)[CH2:5][CH2:4][N:3]1[C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=1.[CH3:27][NH:28][CH2:29][CH2:30][OH:31]>>[OH:31][CH2:30][CH2:29][N:28]([CH3:27])[S:12]([N:9]1[CH2:10][CH2:11][C:6]2([C:2](=[O:1])[N:3]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[CH2:4][CH2:5]2)[CH2:7][CH2:8]1)(=[O:14])=[O:13]
Reactant: O=C1N(c2ccc(OC(F)(F)F)cc2)CCC12CCN(S(=O)(=O)Cl)CC2
Reactant: CNCCO
Product: CN(CCO)S(=O)(=O)N1CCC2(CCN(c3ccc(OC(F)(F)F)cc3)C2=O)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
This material was prepared in analogy to example 285 step B) from 1-Oxo-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decane-8-sulfonyl chloride and 2-methylamino-ethanol. The reaction was subjected to work-up and purification after stirring for 2 h at room temperature. MS (ESI): 452.4 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH:15]([CH3:17])[CH3:16])([CH2:11][CH2:12][CH2:13]Cl)[C:9]#[N:10].[CH3:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:27](=O)([O-])[O-].[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH:15]([CH3:17])[CH3:16])([CH2:11][CH2:12][CH:13]([N:19]([CH3:18])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:27])[C:9]#[N:10]
Reactant: CNCc1ccccc1
Reactant: O=C([O-])[O-]
Reactant: CC(C)C(C#N)(CCCCl)c1ccccc1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(CCC(C#N)(c1ccccc1F)C(C)C)N(C)Cc1ccccc1
Reaction time: 8 h
Yield: 76.6 %

Procedure:
To a mixture of the product compound of Example 8, Step (b) (508 mg, 2.00 mmoles), methyl benzylamine (484 mg, 4.00 mmoles), and tetra-n-butylamrnonium iodide (74 mg) in dry dimethylformamide (2.0 mL) was added anhydrous potassium carbonate (552 mg, 4.00 imol). The mixture was stirred overnight at 80-85°. After cooling, the mixture was partitioned between diethyl ether and water, the aqueous layer was extracted with ether, the combined organic extracts were washed with brine, dried over sodium sulfate, filtered and the solvent evaporated. Chromatography of the residue over silica gel using 25% ethyl acetate-hexane as eluent gave a compound (540 mg) as an oil which was characterized by NMR, as follows: 1H NMR(CD2Cl2) d 7.63-6.95(m, 9H), 1.22(d, 3H), 0.82(d, 3H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][CH2:9][OH:10].[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.[OH-].[Na+]>O>[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:10][CH2:9][CH2:8][CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1
Reactant: BrCCCCCCBr
Reactant: OCCCc1ccccn1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: BrCCCCCCOCCCc1ccccn1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A mixture of 2-pyridinepropanol (15.8 g), 1,6-dibromohexane (60 ml), 50% (w/v) sodium hydroxide (60 ml) and TAB (1.5 g) was stirred at room temperature for 5 h. Water (200 ml) was added and the mixture was extracted with ether (2×200 ml). The organic extracts were washed with water and brine, dried and concentrated to an oil which was purified by FCC eluting with hexane→hexane-ether (1:1) to give the title compound as a colourless oil (18.1 g), t.l.c. (hexane-ether 1:1) Rf 0.19.
Reaction SMILES: O=C(Cl)[O:3][C:4]([Cl:7])(Cl)Cl.[C:9]([Cl:12])(Cl)=O.[NH:13]1C[CH2:17][CH2:16][CH2:15][C:14]1=O>C(OCC)(=O)C>[Cl:12][C:9]1[N:13]([C:4]([Cl:7])=[O:3])[CH2:14][CH2:15][CH2:16][CH:17]=1
Reactant: O=C1CCCCN1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: O=C(Cl)N1CCCC=C1Cl

Procedure:
To stirred diphosgene (3.10 ml, 25.7 mmol) at ˜−20° C. (cooled with a dry ice/2-propanol bath) under nitrogen was added activated carbon (0.25 g), which caused some phosgene gas to be liberated. To the resulting stirred mixture was added very slowly dropwise piperidin-2-one (2.55 g, 25.7 mmol) in ethyl acetate (dried over molecular sieves) (7 ml) over 1 hour, while keeping the temperature below 0° C.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:14]([CH:19]=O)=[CH:15][CH:16]=[CH:17][CH:18]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.ClCCl.C([O-])(O)=O.[Na+]>[C:13]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][N:10]1[CH2:11][CH2:12][N:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][CH2:9]1
Reactant: O=Cc1ccccc1-c1ccccc1
Reactant: c1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: c1ccc(-c2ccccc2CN2CCN(c3ccccc3)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 18.3 %

Procedure:
1-Phenylpiperazine (266 mg, 1.64 mmol) was dissolved in methanol (7 mL) in a reaction vessel and, after adding biphenyl-2-carbaldehyde (150 mg, 0.82 mmol), the mixture was stirred at room temperature for 2 hours. 2 hours later, NaBH(OAc)3 (529 mg, 2.46 mmol) was added and the mixture was further stirred for 8 hours. After the reaction was completed, the reaction solution was diluted with dichloromethane and saturated NaHCO3 solution was added. After extraction, organic layer was dried with anhydrous MgSO4 and then filtered. The filtrate was concentrated and the concentrate was purified by column chromatography (hexane:diethyl ether=8:1) to obtain 50 mg of the target compound (0.15 mmol, 18.3%).
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([S:7]([O-:9])=[O:8])=[CH:3][CH:2]=1.[Na+].[Na+].[I-:13].[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH2:20])=[CH:17][CH:16]=1>CC#N>[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]([I:13])[CH2:20][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=2)(=[O:9])=[O:8])=[CH:17][CH:16]=1
Reactant: Cc1ccc(S(=O)[O-])cc1
Reactant: C=Cc1ccc(Cl)cc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC#N
Product: Cc1ccc(S(=O)(=O)CC(I)c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.8 %

Procedure:
A flask was charged with sodium p-toluenesulfinate (19.28 g, 108 mmol) and NaI (16.22 g, 108 mmol) in dry MeCN (360 mL). The reaction mixture was bubbled through with argon for 15 min followed by addition of 4-chlorostyrene (9.09 mL, 72.2 mmol) and (NH4)2Ce(NO3)6 (79 g, 144 mmol). The reaction mixture was stirred for 18 h under argon atmosphere at room temperature. Then the solvent was evaporated under reduced pressure and the residue was partitioned between H2O (400 mL) and DCM (500 mL). The layers were separated and the aqueous phase was extracted with DCM (200 mL). The organic layer was washed with saturated aqueous Na2S2O3 (150 mL), brine (150 mL), dried over Na2SO4, filtered and evaporate to dryness to afford 28.5 g (94%) of the desired product.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].C12(O)CC3CC(CC(O)(C3)C1)C2.C(OC=C)(=O)C.[CH:25]([O:27][C:28]12[CH2:37][CH:32]3[CH2:33][CH:34]([CH2:36][C:30]([O:38]C=C)([CH2:31]3)[CH2:29]1)[CH2:35]2)=[CH2:26]>C1(C)C=CC=CC=1>[CH:25]([O:27][C:28]12[CH2:37][CH:32]3[CH2:33][CH:34]([CH2:36][C:30]([OH:38])([CH2:31]3)[CH2:29]1)[CH2:35]2)=[CH2:26]
Reactant: C=COC12CC3CC(C1)CC(OC=C)(C3)C2
Agent: O=C([O-])[O-]
Agent: OC12CC3CC(C1)CC(O)(C3)C2
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: C=COC(C)=O
Product: C=COC12CC3CC(CC(O)(C3)C1)C2
Temperature: 100 °C
Reaction time: 5 h

Procedure:
To a mixture of di-μ-chlorobis(1,5-cyclooctadiene)diiridium(I) [Ir(cod)Cl]2 (6.7 mg, 0.01 mmol) and sodium carbonate (64 mg, 0.6 mmol) in toluene (1.0 ml), 1,3-adamantanediol (1 mmol) and vinyl acetate (6 mmol) were added, followed by stirring at 100° C. in an atmosphere of argon gas for 5 hours. The reaction mixture was analyzed by gas chromatography to find that 1,3-bis(vinyloxy)adamantane and 3-vinyloxy-1-adamantanol were produced in yields of 41% and 16%, respectively, with a conversion from 1,3-adamantanediol of 97%.
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].C(N(CC)CC)C.[C:20]([NH2:24])([CH3:23])([CH3:22])[CH3:21].Cl.[CH:26]1[C:36]2[CH:35]=[CH:34][C:33]3[CH:37]=[CH:38][CH:39]=[CH:40][C:32]=3[C:31](=[C:41]3[CH2:46][CH2:45][N:44]([C:47](=[O:50])[CH2:48][NH2:49])[CH2:43][CH2:42]3)[C:30]=2[CH:29]=[CH:28][CH:27]=1>O1CCCC1>[C:20]([NH:24][C:1]([NH:49][CH2:48][C:47]([N:44]1[CH2:43][CH2:42][C:41](=[C:31]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:36]=3[CH:35]=[CH:34][C:33]3[CH:37]=[CH:38][CH:39]=[CH:40][C:32]2=3)[CH2:46][CH2:45]1)=[O:50])=[O:2])([CH3:23])([CH3:22])[CH3:21]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: NCC(=O)N1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1
Reactant: CC(C)(C)N
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)NC(=O)NCC(=O)N1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1
Reaction time: 1 h

Procedure:
89.2 mg (0.55 mmol) of 1,1′-carbonylbis-1H-imidazole and 25.3 mg (0.25 mmol) of triethylamine were dissolved in 2.5 ml of tetrahydrofuran. A solution of 36.6 mg (0.50 mmol) of t-butylamine in 1 ml of tetrahydrofuran was slowly added to the resultant solution at 0° C. in argon stream. After stirring for 1 hour, a solution of 110.7 mg (0.30 mmol) of 2-[4-(5H-dibenzo[a,d][7]annulen-5-ylidene)-1-piperidinyl]-2-oxoethanamine hydrochloride and 30.3 mg (0.30 mmol) of triethylamine in 1 ml of tetrahydrofuran was slowly added thereto. After stirring for 2 hours, the solvent was evaporated and the product was purified by the silica gel chromatography (hexane:ethyl acetate=85:15 to 3:2) to obtain the title compound.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][C:20]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[CH:15]1([C:13]([NH:12][C:7]2[N:8]=[CH:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([C:20]2[CH:21]=[C:22]([CH:26]=[CH:27][C:19]=2[CH3:18])[C:23]([OH:25])=[O:24])[CH:11]=3)=[O:14])[CH2:17][CH2:16]1
Reactant: Cc1ccc(C(=O)O)cc1B1OC(C)(C)C(C)(C)O1
Reactant: O=C(Nc1cc2ccc(Br)cc2cn1)C1CC1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Cc1ccc(C(=O)O)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
Temperature: 90 °C
Yield: 93 %

Procedure:
A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (0.3305 g, 1.135 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.3782 g, 1.443 mmol), potassium carbonate (0.3196 g, 2.312 mmol), and bis(di-tert-butyl(4-dimethylaminophenyephosphine)dichloropalladium(II) (81.9 mg, 0.116 mmol) in 1,4-dioxane (5.0 mL, 64 mmol) and water (0.5 mL, 30 mmol) was heated at 90° C. for 2 hours. The reaction mixture was cooled to room temperature, acidified with 10% aqueous citric acid, and extracted twice with ethyl acetate. The combined organic extracts were reduced in volume under evaporation and the product collected via filtration as a white precipitate and dried under vacuum to yield 365.5 mg (91%) of 3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzoic acid. LCMS (ESI): M+H=347.2; 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.04 (s, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.89-7.83 (m, 2H), 7.72 (d, J=8.5 Hz, 1H), 7.45 (d, J=7.7 Hz, 1H), 2.34 (s, 3H), 2.14-2.02 (m, 1H), 0.85 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5](I)=[CH:4][N:3]=1.[NH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:23])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CC1(C)C(C)(C)OB([C:32]2[S:33][CH:34]=[CH:35][CH:36]=2)O1>>[Cl:1][C:2]1[N:7]=[C:6]([NH:10][CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:5]([C:32]2[S:33][CH:34]=[CH:35][CH:36]=2)=[CH:4][N:3]=1
Reactant: Clc1ncc(I)c(Cl)n1
Reactant: CC1(C)OB(c2cccs2)OC1(C)C
Reactant: NCCCNC(=O)Cc1ccccc1
Product: O=C(Cc1ccccc1)NCCCNc1nc(Cl)ncc1-c1cccs1

Procedure:
Preparation according to procedures 2 and 3 with the use of 2,4-dichloro-5-iodopyrimidine, N-(3-amino-propyl)-2-phenyl-acetamide and 4,4,5,5-tetramethyl-2-(2-thienyl)-1,3,2-dioxaborolane.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][NH:13][CH2:12][CH:11]([C:15]([O:17][CH3:18])=[O:16])[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:28](Cl)(=[O:39])[O:29][C:30]1[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=1>ClCCl>[F:20][C:2]([F:19])([F:1])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][N:13]([C:28]([O:29][C:30]3[CH:31]=[CH:32][C:33]([N+:36]([O-:38])=[O:37])=[CH:34][CH:35]=3)=[O:39])[CH2:12][CH:11]([C:15]([O:17][CH3:18])=[O:16])[CH2:10]2)=[CH:5][CH:4]=1
Reactant: COC(=O)C1CNCC(c2ccc(C(F)(F)F)cc2)C1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C1CC(c2ccc(C(F)(F)F)cc2)CN(C(=O)Oc2ccc([N+](=O)[O-])cc2)C1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
20.0 g (69.6 mmol) of the compound from Example 53A were dissolved in 1.0 l of dichloromethane, and 14.1 g (139 mmol) of triethylamine were added at 0° C. 14.0 g (69.6 mmol) of 4-nitrophenyl chlorocarbonate were then added dropwise. The reaction mixture was stirred at 0° C. for 2 h and then at RT for 16 h. For workup, the mixture was washed with saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. This gave 31.3 g of crude product, which was reacted without any further purification steps.
Reaction SMILES: C[O-].[Na+].[Na].[CH:5](=[N:12][NH:13][C:14](N)=[NH:15])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(O[C:20](=[O:29])[CH2:21][NH:22][CH2:23][C:24]([O:26][CH2:27]C)=[O:25])C>CO.C(Cl)(Cl)Cl.O>[CH:5](=[N:12][N:13]=[C:14]1[NH:15][C:20](=[O:29])[CH2:21][N:22]1[CH2:23][C:24]([O:26][CH3:27])=[O:25])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: N=C(N)NN=Cc1ccccc1
Reactant: CCOC(=O)CNCC(=O)OCC
Agent: C[O-]
Agent: [Na+]
Agent: [Na]
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: O
Product: COC(=O)CN1CC(=O)NC1=NN=Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 27.1 %

Procedure:
To a methanol solution of sodium methoxide prepared by dissolving 2.30 g of metal sodium in 150 ml of methanol was added 5.70 g of benzylideneaminoguanidine, and, after stirring the mixture for one hour at room temperature, 11.35 g of iminodiacetic acid diethyl ester was added thereto, followed by refluxing under heating for 17 hours. After cooling the reaction mixture, water and chloroform were added thereto to distribute the mixture between aqueous and organic layers and, then, the aqueous layer was extracted three times with chloroform. The organic layer was combined with the extract. After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure, and the residue was charged on silica gel column chromatography, followed by elution with a mixed solvent of chloroform and methanol (100:1 (v/v)). Thus 2.61 g of 2-benzylidenehydrazono-1-methoxycarbonylmethylimidazolidin-4-one was obtained.