Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:26]=[C:25]([N+:27]([O-])=O)[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[O:15])[S:13][C:6]=12.[Cl-].[NH4+]>CO.O.[Zn]>[NH2:27][C:25]1[CH:24]=[CH:23][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[O:15])[S:13][C:6]=23)=[C:2]([F:1])[CH:26]=1
Reactant: CN1CCN(C(=O)c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)CC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Solvent: CO
Product: CN1CCN(C(=O)c2cc3nccc(Oc4ccc(N)cc4F)c3s2)CC1
Temperature: 25 °C
Yield: 65.6 %

Procedure:
Zinc (0.75 g, 11.53 mmol) was added to a suspension of 437 (1.2 g, 2.88 mmol) and ammonium chloride (0.31 g, 5.76 mmol) in a mixture of MeOH (30 mL) and water (5.10 mL). The suspension was heated to reflux for 50 min. After cooling to room temperature, the reaction mixture was filtered and concentrated. The residue was partitioned between DCM, water and ammonium hydroxide. The organic layer was collected, successively washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by biotage (SNAP 50 g cartridge; MeOH/DCM: 0/100 to 20/80 over 30CV), to afford the title compound 438 (733 mg, 1.89 mmol, 66% yield) as a yellow solid. MS (m/z): 387.4 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[CH2:11]O)[CH:5]=[C:6]([F:8])[CH:7]=1.P(Br)(Br)[Br:14].O>CCOCC>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4](/[CH:9]=[CH:10]/[CH2:11][Br:14])[CH:3]=1
Reactant: OC/C=C/c1cc(F)cc(Br)c1
Reactant: BrP(Br)Br
Solvent: CCOCC
Solvent: O
Product: Fc1cc(Br)cc(/C=C/CBr)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 4.2 g (0.0182 mol) of (E)-3-(3-bromo-5-fluorophenyl)-2-propen-1-ol in 65 ml of anhydrous ether is cooled to 0° C. under a nitrogen atmosphere. 3.3 g (0.0121 mol) of phosphorus tribromide are added dropwise and then the mixture is stirred for 1 h at 0° C. and left to return to room temperature overnight. The mixture is poured into water and extraction with ether, washing with water, drying over sodium sulphate, filtration and concentration under vacuum are carried out.
Reaction SMILES: [CH2:1]([O:8][CH:9]([CH3:15])[CH2:10][CH2:11][C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.Cl.[NH2:28][C:29]1[C:37]([OH:38])=[C:36]2[C:32]([CH2:33][CH2:34][CH:35]2[CH2:39][CH2:40][NH:41][C:42](=[O:44])[CH3:43])=[CH:31][CH:30]=1>O1CCCC1.N1C=CC=CC=1>[C:42]([NH:41][CH2:40][CH2:39][CH:35]1[C:36]2[C:32](=[CH:31][CH:30]=[C:29]([NH:28][C:12](=[O:14])[CH2:11][CH2:10][CH:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH3:15])[C:37]=2[OH:38])[CH2:33][CH2:34]1)(=[O:44])[CH3:43]
Reactant: CC(CCC(=O)O)OCc1ccccc1
Reactant: CC(=O)NCCC1CCc2ccc(N)c(O)c21
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: c1ccncc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(=O)NCCC1CCc2ccc(NC(=O)CCC(C)OCc3ccccc3)c(O)c21
Reaction time: 0.5 h
Yield: 57.4 %

Procedure:
4-(Benzyloxy)pentanoic acid (230 mg, 1.10 mmol) was dissolved in tetrahydrofuran (10 mL), oxalyl chloride (90 μL, 1.05 mmol) and dimethylformamide (10 μL) were added under ice-cooling, and the mixture was stirred for 30 min. The solvent was evaporated under reduced pressure, and the residue was diluted with dichloromethane (1 mL). This was added to a solution of N-[2-(6-amino-7-hydroxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide hydrochloride (244 mg, 0.903 mmol) in pyridine (10 mL) under ice-cooling, and the mixture was stirred at room temperature for 15 min. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=80/20→100/0) to give the title compound (220 mg, yield 57%).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[C:9]([CH2:10][OH:11])=[C:8]([CH3:12])[N:7]=[C:6]([S:13][CH3:14])[N:5]=1)[CH3:2]>C(Cl)(Cl)Cl.[O-2].[Mn+2]>[CH2:1]([NH:3][C:4]1[C:9]([CH:10]=[O:11])=[C:8]([CH3:12])[N:7]=[C:6]([S:13][CH3:14])[N:5]=1)[CH3:2]
Reactant: CCNc1nc(SC)nc(C)c1CO
Agent: [Mn+2]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: CCNc1nc(SC)nc(C)c1C=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 93.6 %

Procedure:
To a solution of [4-(ethylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl]methanol (41.0 g) in chloroform (4000 mL) was added manganese oxide (125 g, 1.4 mole) and stirred for 4 h at room temperature. More manganese oxide was added until the disappearance of alcohol compound was observed. The reaction mixture was filtered through Celite and washed with some chloroform and evaporated all organic solvents to give 38 g (92% yield) of 4-(ethylamino)-6-methyl-2-(methylthio)pyrimidine-5-carbaldehyde as a colorless solid, which was used without purification in the next step.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@H:4]1[CH2:8][CH2:7][CH2:6][NH:5]1.N[CH2:10][C@@H:11]1CC[CH2:13][N:12]1CC.C(=O)C>>[CH3:1][O:2][CH2:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:10][CH2:11][NH:12][CH3:13]
Reactant: COC[C@H]1CCCN1
Reactant: CCN1CCC[C@H]1CN
Agent: CC=O
Product: CNCCN1CCC[C@@H]1COC

Procedure:
By using O-methyl-D-prolinol (500 mg) as a starting material, the title compound (0.45 g) was obtained in the same manners as those of Reference Example 1, (1) and Reference Example 39, (2).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]1[C@H:24]([C:25]([NH:27][C:28]2[CH:29]=[C:30]([C:34]3[N:35]=[C:36]([S:39][CH2:40][C:41]([NH:43][CH:44]4[CH2:49][CH2:48][N:47]([CH2:50][C:51]5[CH:56]=[CH:55][C:54]([Cl:57])=[C:53]([Cl:58])[CH:52]=5)[CH2:46][CH2:45]4)=[O:42])[S:37][CH:38]=3)[CH:31]=[CH:32][CH:33]=2)=[O:26])[CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1)=O)(C)(C)C>C(Cl)(Cl)Cl>[Cl:58][C:53]1[CH:52]=[C:51]([CH:56]=[CH:55][C:54]=1[Cl:57])[CH2:50][N:47]1[CH2:48][CH2:49][CH:44]([NH:43][C:41](=[O:42])[CH2:40][S:39][C:36]2[S:37][CH:38]=[C:34]([C:30]3[CH:31]=[CH:32][CH:33]=[C:28]([NH:27][C:25]([C@@H:24]4[CH2:23][C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[CH2:16][NH:15]4)=[O:26])[CH:29]=3)[N:35]=2)[CH2:45][CH2:46]1
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)Nc1cccc(-c2csc(SCC(=O)NC3CCN(Cc4ccc(Cl)c(Cl)c4)CC3)n2)c1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: O=C(CSc1nc(-c2cccc(NC(=O)[C@@H]3Cc4ccccc4CN3)c2)cs1)NC1CCN(Cc2ccc(Cl)c(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 62.4 %

Procedure:
Trifluoroacetic acid (5 mL) was added to the product (667 mg) of Example 54, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with chloroform (100 mL), and the mixture was washed with 1 mol/L sodium hydroxide and saturated brine, and dried. The solvent was evaporated under reduced pressure to give the title compound (362 mg) as a white amorphous solid.
Reaction SMILES: [C:1]([C:4]1[NH:20][C:7]2=[CH:8][C:9]3[C:10]([CH3:19])([CH3:18])[C:11](=[O:17])[N:12]([CH2:15][CH3:16])[C:13]=3[CH:14]=[C:6]2[N:5]=1)(=[O:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:33]1[CH:38]=[CH:37][CH2:36][CH2:35][CH2:34]1>ClCCl>[C:1]([C:4]1[N:20]([CH:34]2[CH2:35][CH2:36][CH2:37][CH2:38][O:33]2)[C:7]2=[CH:8][C:9]3[C:10]([CH3:19])([CH3:18])[C:11](=[O:17])[N:12]([CH2:15][CH3:16])[C:13]=3[CH:14]=[C:6]2[N:5]=1)(=[O:3])[CH3:2]
Reactant: CCN1C(=O)C(C)(C)c2cc3[nH]c(C(C)=O)nc3cc21
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Product: CCN1C(=O)C(C)(C)c2cc3c(cc21)nc(C(C)=O)n3C1CCCCO1
Yield: 44.4 %

Procedure:
2-Acetyl-5-ethyl-7,7-dimethyl-5,7-dihydro-1H-imidazo[4,5-f]indol-6-one (11.7 g, 43.1 mmol) and p-toluenesulfonic acid monohydrate (0.82 g, 4.3 mmol) were dissolved in dichloromethane (200 mL). To this solution 3,4-dihydro-2H-pyrane (4.81 g, 56 mmol) was added and the mixture stirred at reflux for 24 h. The mixture was filtered, the filtrate washed with water (2×100 mL), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica (dichloromethane/methanol 93:3) yielding 6.8 g (44%) of a light yellow solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19](Cl)[N:18]=[C:17]([CH3:31])[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Na].[CH2:33]([OH:37])[CH2:34][CH2:35][OH:36]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:36][CH2:35][CH2:34][CH2:33][OH:37])[N:18]=[C:17]([CH3:31])[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: OCCCO
Reactant: COc1ccccc1Oc1c(Cl)nc(C)nc1NS(=O)(=O)c1ccc(C(C)(C)C)cc1
Agent: [Na]
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(C)nc1OCCCO

Procedure:
By reacting p-tert-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-methyl-4-pyrimidinyl]benzenesulfonamide with the monosodium salt of 1,3-propanediol, there was obtained p-tert-butyl-N-[6-(3-hydroxypropoxy)-5-(o-methoxyphenoxy)-2-methyl-4-pyrimidinyl]benzenesulfonamide as a white foam.
Reaction SMILES: [Br:1]Br.[OH:3][C@@H:4]1[C@@H:23]([O:24][CH2:25][CH3:26])[CH2:22][C@@:21]2([CH3:27])[C@@H:6]([CH2:7][CH2:8][C@@H:9]3[C@@H:20]2[C:19](=[O:28])[CH2:18][C@@:17]2([CH3:29])[C@H:10]3[CH2:11][CH2:12][C@@H:13]2[C:14](=[O:16])[CH3:15])[CH2:5]1.C(Cl)(=O)C.O>CO>[Br:1][CH2:15][C:14](=[O:16])[C@@H:13]1[C@:17]2([CH3:29])[C@H:10]([C@H:9]3[C@H:20]([C:19](=[O:28])[CH2:18]2)[C@:21]2([CH3:27])[C@H:6]([CH2:5][C@H:4]([OH:3])[C@@H:23]([O:24][CH2:25][CH3:26])[CH2:22]2)[CH2:7][CH2:8]3)[CH2:11][CH2:12]1
Reactant: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]32)C[C@@H]1O
Reactant: BrBr
Solvent: CO
Solvent: CC(=O)Cl
Solvent: O
Product: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(=O)CBr)[C@@]4(C)CC(=O)[C@@H]32)C[C@@H]1O
Reaction time: 2 h

Procedure:
Bromine (0.53 g.) in methanol (1.45 ml.) was added dropwise to a stirred solution of 3α-hydroxy-2β-ethoxy-5α-pregnane-11,20-dione (2.0 g) in methanol (15 ml) containing a trace of acetyl chloride at 0°. The addition took 2 hr. and the clear solution was then poured into water and collected by filtration, washed with water and dried in vacuo to give title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH:14]C(OC)=O)=[N:10]2)=[CH:5][CH:4]=1.[OH-].[K+].Cl>O.CO.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH2:14])=[N:10]2)=[CH:7][CH:8]=1
Reactant: COC(=O)Nc1ccn(-c2ccc(OC)cc2)n1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(-n2ccc(N)n2)cc1
Temperature: 70 °C
Reaction time: 4 h
Yield: 94.4 %

Procedure:
To a solution of 1-[(4-methoxy)phenyl]-3-[(methoxycarbonyl)amino]-1H-pyrazole-5-[(2′-aminosulfonyl-[1,1′]-biphen-4-yl)carboxyamide (0.22 g, 0.42 mmol) in 10 mL of 1:1 water/methanol was added potassium hydroxide (2.0 g, 35 mmol). The resulting mixture was stirred at 70° C. for 4 h and then was cooled to ambient temperature and was acidified with aq HCl. The reaction mixture was diluted with ethyl acetate and the organics were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford 75 mg (38%) of the title compound as a white powder. LRMS (ES+): 463.8 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[C:9](=[O:14])[O:10][C:11](=[O:13])[NH:12][C:7]=2[CH:6]=[CH:5][CH:4]=1.C1C(=O)N([Br:22])C(=O)C1>CN(C=O)C.ClCCl>[Br:22][C:4]1[CH:5]=[CH:6][C:7]2[NH:12][C:11](=[O:13])[O:10][C:9](=[O:14])[C:8]=2[C:3]=1[O:2][CH3:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1cccc2[nH]c(=O)oc(=O)c12
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1c(Br)ccc2[nH]c(=O)oc(=O)c12
Temperature: 25 °C
Reaction time: 8 h
Yield: 135.1 %

Procedure:
A solution of Example 385A (10.5 g, 54.4 mmol) in DMF (100 mL) and dichloromethane (200 mL) was cooled to 0° C., treated portionwise with NBS (14.4 g, 80.9 mmol) over 40 minutes, stirred overnight at room temperature and filtered. The filtrate was concentrated to provide the desired product (˜20 g) which was used directly in the next step.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]([C:10]1[S:11][CH:12]=[C:13]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][CH2:18]2)=[O:16])[N:14]=1)[CH3:9])(C)(C)C.[ClH:28].O1CCOCC1>>[ClH:28].[NH2:7][CH:8]([C:10]1[S:11][CH:12]=[C:13]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][CH2:18]2)=[O:16])[N:14]=1)[CH3:9]
Reactant: CC(NC(=O)OC(C)(C)C)c1nc(C(=O)N2CCCc3ccccc32)cs1
Agent: Cl
Solvent: C1COCCO1
Product: CC(N)c1nc(C(=O)N2CCCc3ccccc32)cs1
Temperature: 25 °C

Procedure:
A solution of tert-butyl(1-(4-(1,2,3,4-tetrahydroquinoline-1-carbonyl)thiazol-2-yl)ethyl)-carbamate (180 mg, 0.47 mmol) in 4N hydrogen chloride/dioxan (10 ml) was stirred in an ice/water bath and allowed to warm to room temperature. The mixture was concentrated and azeotroped with toluene twice, tetrachloromethane twice and dichloromethane once to afford 1-(2-(1-aminoethyl)thiazole-4-carbonyl)-1,2,3,4-tetrahydroquinoline hydrochloride. The yield was assumed to be quantitative and the material was used directly by taking up in dichloromethane (5 ml) and triethylamine (0.16 ml, 118 mg, 1.2 mmol). The resulting solution was cooled in an ice/water bath and to it was added 4-bromobenzenesulphonyl chloride (119 mg, 0.47 mmol). The mixture was allowed to warm to room temperature and stirred for 18 h. Evaporation and chromatography (50% EtOAc/50% hexanes) afforded 1-(2-(1-(4-bromobenzenesulphonylamino)ethyl)thiazole-4-carbonyl)-1,2,3,4-tetrahydroquinoline as a white solid (144 mg, 61%).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[N+:11]([O-])=O>[Pd]>[NH2:11][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:3]=1[NH:2][CH3:1])[C:7]#[N:8]
Reactant: CNc1ccc(C#N)cc1[N+](=O)[O-]
Agent: [Pd]
Product: CNc1ccc(C#N)cc1N
Yield: 0.1 %

Procedure:
3-Amino-4-methylamino-benzonitrile (1.23 mg) was prepared by following General Procedure B starting from 4-methylamino-3-nitro-benzonitrile (1.33 g) and Pd/C (10% by weight, 133 mg). The crude product was used in the next step without further purification.
Reaction SMILES: [CH3:1][O-:2].[Na+].[Cl:4][C:5]1[CH:10]=[C:9](Cl)[N:8]=[CH:7][N:6]=1.O>CO>[Cl:4][C:5]1[CH:10]=[C:9]([O:2][CH3:1])[N:8]=[CH:7][N:6]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1cc(Cl)ncn1
Temperature: 25 °C
Yield: 85.9 %

Procedure:
8 g sodium methanolate was added to 10 g 4,6-dichlorpyrimidine in 100 mL methanol at 0° C. The reaction was stirred at RT over night. The mixture was added into water and extracted with ethylacetate. The organic layer was dried with magnesium sulfate and evaporated to give 8.34 g desired product. Rt: 0.97 min (method B), (M+H)+: 145
Reaction SMILES: BrC1C2N(N=C(Cl)N=2)C=CC=1.C1(C)C=CC(N2C=C(B(O)O)C=N2)=CC=1.[Cl:27][C:28]1[N:48]=[C:31]2[C:32]([C:36]3[CH:37]=[N:38][N:39]([C:41]4[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=4)[CH:40]=3)=[CH:33][CH:34]=[CH:35][N:30]2[N:29]=1.[C:49]([O:53][C:54]([N:56]1[CH2:61][CH2:60][CH:59]([C:62]2[CH:67]=[CH:66][C:65]([NH2:68])=[CH:64][CH:63]=2)[CH2:58][CH2:57]1)=[O:55])([CH3:52])([CH3:51])[CH3:50].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[Cl:27][C:28]1[N:48]=[C:31]2[C:32]([C:36]3[CH:37]=[N:38][N:39]([C:41]4[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=4)[CH:40]=3)=[CH:33][CH:34]=[CH:35][N:30]2[N:29]=1.[C:49]([O:53][C:54]([N:56]1[CH2:61][CH2:60][CH:59]([C:62]2[CH:67]=[CH:66][C:65]([NH:68][C:28]3[N:48]=[C:31]4[C:32]([C:36]5[CH:37]=[N:38][N:39]([C:41]6[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=6)[CH:40]=5)=[CH:33][CH:34]=[CH:35][N:30]4[N:29]=3)=[CH:64][CH:63]=2)[CH2:58][CH2:57]1)=[O:55])([CH3:52])([CH3:50])[CH3:51]
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Agent: Cc1ccc(-n2cc(-c3cccn4nc(Cl)nc34)cn2)cc1
Agent: Cc1ccc(-n2cc(B(O)O)cn2)cc1
Agent: Clc1nc2c(Br)cccn2n1
Product: Cc1ccc(-n2cc(-c3cccn4nc(Nc5ccc(C6CCN(C(=O)OC(C)(C)C)CC6)cc5)nc34)cn2)cc1

Procedure:
2-Chloro-8-(1-p-tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine and 1-p-tolyl-pyrazole-4-boronic acid in a manner analogous to Example 2c (0.40 g, 68%). 287b) 4-{4-[8-(1-p-Tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester was prepared from 2-chloro-8-(1-p-tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine and 4-(4-amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester with 2,2′-bis-dicyclohexylphosphanyl-biphenyl as the ligand in a manner analogous to Example 2d (0.265 g, 40%). MP=124-125° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.60 (s, 1H), 9.24 (s, 1H), 8.68 (d, 1H), 8.64 (s, 1H), 7.98 (m, 1H), 7.77 (m, 2H), 7.66 (m, 2H), 7.40 (m, 2H), 7.21 (m, 2H), 4.08 (m, 2H), 2.80 (m, 2H), 2.62 (m, 1H), 2.38 (s, 3H), 1.73 (m, 2H), 1.48 (m, 2H), 1.41 (s, 3H). MS=550 (MH)+.
Reaction SMILES: Cl[C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[C:3]=1[CH:12]=[O:13].C(N(CC)CC)C.[C:21]1([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>ClCCl>[CH3:8][N:7]1[C:2]([N:30]2[CH2:31][CH2:32][N:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:28][CH2:29]2)=[C:3]([CH:12]=[O:13])[C:4](=[O:11])[N:5]([CH3:10])[C:6]1=[O:9]
Reactant: Cn1c(Cl)c(C=O)c(=O)n(C)c1=O
Reactant: c1ccc(N2CCNCC2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cn1c(N2CCN(c3ccccc3)CC2)c(C=O)c(=O)n(C)c1=O
Temperature: 25 °C

Procedure:
To an ice-cooled, stirred solution of 6-chloro-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde (0.600 g, 2.96 mmol) and triethyl-amine (0.45 ml, 3.26 mmol) in dichloromethane (20 ml), a solution of N-phenylpiperazine (0.49 ml, 3.26 mmol) in dichloromethane (10 ml) was added dropwise. The resulting suspension was stirred at room temperature until the starting material was consumed (3.5 h, monitored by TLC). Then the reaction mixture was washed with water (3×10 ml), and the organic phase was dried over 20, anhydrous MgSO4. The solvent was evaporated in vacuo, and the brown oily crude product was purified by column chromatography with a mixture of dichloromethane:ethyl acetate (1:1) as the eluent and crystallized from ethanol.
Reaction SMILES: [Na].CO.Cl.[NH2:5][C:6]([NH2:8])=[NH:7].Cl.[Cl:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[N:15]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[C:24]([CH3:32])[CH:23]=2)[CH:14]=1)=[O:12]>O1CCCC1.ClCCl>[ClH:10].[CH3:32][C:24]1[CH:23]=[C:22]([N:15]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:21]3[C:13]([C:11]([NH:7][C:6]([NH2:8])=[NH:5])=[O:12])=[CH:14]2)[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1
Reactant: N=C(N)N
Reactant: Cc1cc(-n2cc(C(=O)Cl)c3cccnc32)c2ccccc2n1
Agent: Cl
Agent: [Na]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(-n2cc(C(=O)NC(=N)N)c3cccnc32)c2ccccc2n1
Temperature: 20 °C
Reaction time: 2 h
Yield: 13.1 %

Procedure:
0.43 g (19 mmol) of sodium was added portionwise, at a temperature in the region of 20° C. under an argon atmosphere, to 30 cm3 of methanol and then, after the sodium has been completely consumed, 1.9 g (20 mmol) of guanidine hydrochloride were added. The reaction mixture was stirred at a temperature in the region of 20° C. for 2 h, then it was concentrated to dryness under reduced pressure (2.7 kPa) and the residue was 2 times in succession taken up in 10 cm3 of dichloromethane (stabilized over amylene) and the supernatant separated. The residue was subsequently concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained was taken up in 40 cm3 of a 1:1 mixture of dichloromethane (stabilized over amylene) and tetrahydrofuran under an argon atmosphere at a temperature in the region of 20° C. and 1.1 g (3.4 mmol) of 3-chlorocarbonyl-1-(2-methylquinolin-4-yl)-1H-pyrrolo[2,3-b]pyridine hydrochloride, in suspension in 20 cm3 of a 1:1 mixture of dichloromethane (stabilized over amylene) and tetrahydrofuran, were added with stirring. After stirring at a temperature in the region of 20° C. for 65 h, the reaction mixture was concentrated to dryness under reduced pressure (2.7 kPa). The residue was taken up in 30 cm3 of ethanol and the mixture was heated at reflux for 5 minutes and then reconcentrated to dryness under reduced pressure (2.7 kPa). The residue was taken up in 50 cm3 of water and extracted successively with 50 cm3 and then 25 cm3 of ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa). The residue was purified by flash chromatography on a column of silica gel (0.06–0.20 mm), elution being carried out with a dichloromethane/methanol (95/5 by volume) mixture. The fractions comprising the expected product were combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue was triturated in 10 cm3 of diisopropyl ether, filtered off, washed twice with 5 cm3 of diisopropyl ether and dried under reduced pressure (2.7 kPa) at a temperature in the region of 50° C. 0.17 g of N-[1-(2-methylquinolin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]guanidine hydrochloride was thus obtained in the form of a yellow crystalline solid melting at 178° C. (Analysis C19H16N6O.HCl % calculated C, 59.92; H, 4.50; N, 22.07; O, 4.20%. found C, 60.40; H, 4.50; N, 21.47).
Reaction SMILES: [CH2:1]([N:8]=[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P(C1C=C(C)C=C(C)C=1)C1C=C(C)C=C(C)C=1)C.C(O)(=O)C.[H][H]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH2:1]([NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [H][H]
Reactant: CC(=NCc1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CCP(c1cc(C)cc(C)c1)c1cc(C)cc(C)c1
Agent: [I-]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CC(NCc1ccccc1)c1ccccc1
Reaction time: 0.33 h

Procedure:
The process is carried out as in Example 6, but the reaction conditions are modified as follows: 0.636 g (3 mmol) of N-benzyl-N-(1-phenylethylidene)amine, 10.2 mg (0.0152 mmol) of [Ir(1,5-cyclooctadiene)Cl]2, 21.4 mg (0.0333 mmol) of {(R)-1-[(S)-2-diphenylphosphino)ferrocenyl]}ethyl-di(3,5-dimethylphenyl)phosphine (ligand) and 15 mg (0.04 mmol) of tetrabutylammonium iodide, 2 ml of acetic acid, 15 ml of toluene, 30 bar of hydrogen, reaction temperature: 25° C. The reaction time is 20 minutes. The conversion is complete, the ee 31%.
Reaction SMILES: Cl[Si](C)(C)[CH3:3].[NH2:6][C@H:7]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C@H:8]1[C:14]([OH:16])=[O:15]>CO>[CH3:3][O:15][C:14]([C@@H:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C@@H:7]1[NH2:6])=[O:16]
Reactant: N[C@H]1CCCCC[C@H]1C(=O)O
Reactant: C[Si](C)(C)Cl
Solvent: CO
Product: COC(=O)[C@@H]1CCCCC[C@@H]1N
Reaction time: 2 h
Yield: 61.8 %

Procedure:
Chlorotrimethylsilane (3.96 mL, 31.2 mmol) was added dropwise to cis-2-aminocycloheptanecarboxylic acid (2.45 g, 15.6 mmol) in methanol (25 mL) at room temperature under nitrogen. After stirring for 2 h, the solvent was evaporated in vacuo and the residue was triturated with ether. The white solid was filtered and then dried under vacuum overnight to provide (1.65 g) cis-2-aminocycloheptanecarboxylic acid methyl ester: 1H NMR (CDCl3) δ 8.44 (s br, 2 H), 3.77 (s, 3 H), 3.62 (s br, 1 H), 3.27 (s br, 1 H), 2.20 (m, 2 H), 1.71 (m, 2 H), 1.66–1.47 (m, 6 H); MS m/e 172.26 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:6]3[CH2:15][CH2:14][CH2:13][CH:7]3[C:8](=S)[NH:9][C:10]=2[CH:11]=1.[NH3:16]>>[NH2:16][C:8]1[CH:7]2[CH2:13][CH2:14][CH2:15][CH:6]2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:11][C:10]=2[N:9]=1
Reactant: N
Reactant: Fc1ccc2c(c1)NC(=S)C1CCCC21
Product: NC1=Nc2cc(F)ccc2C2CCCC12
Yield: 99 %

Procedure:
Analogously to Example 4, 7-Fluoro-1,2,3,3a,5,9b-hexahydrocyclopenta[c]quinoline-4-thione (170 mg, 0.77 mmol) in 7N methanolic ammonia solution (20 ml) is reacted to form 160 mg (99%) of product.