Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N.[OH-:2].[K+].[C:4]([C:23]#[N:24])([C:7]([C:10]([C:13]([C:16]([C:19]([F:22])([F:21])[F:20])([F:18])[F:17])([F:15])[F:14])([F:12])[F:11])([F:9])[F:8])([F:6])[F:5]>>[F:5][C:4]([F:6])([C:7]([F:9])([F:8])[C:10]([F:12])([F:11])[C:13]([F:15])([F:14])[C:16]([F:17])([F:18])[C:19]([F:20])([F:21])[F:22])[C:23]([NH2:24])=[O:2]
Reactant: [OH-]
Reactant: N#CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: N
Agent: [K+]
Product: NC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Yield: 98.5 %

Procedure:
A ten-fold excess, fifty (50) ml, of anhydrous ammonia gas were condensed into a four-neck flask fitted with an agitator, reflux condenser, dropping funnel, thermometer, and a drying tube (filled with solid KOH) which had been cooled in a dry ice/ethanol bath. The ammonia was condensed into the flask via the drying tube. With good agitation and cooling, 60 g of a reaction product (perfluoroheptanonitrile), made in accordance with the technique described in Example 4 for conversion of a perfluoroacid to a nitrile, having the structure C6F13CN was added slowly. After addition was completed, the temperature was allowed to slowly rise to ambient allowing the excess ammonia to evaporate. The resulting white solid product was air dried to yield 62.0 g of perfluoroheptanamide having the following formula (a yield of 98.5% with a m.p. at 75-76° C.).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]2[N:16]([CH3:20])[N:17]=[N:18][CH:19]=2)[CH2:9][C:10]([O:12]CC)=[O:11])=[CH:4][CH:3]=1.Br[CH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]2([CH3:36])[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+].[Li+].[OH-]>CN(C=O)C.O>[CH3:20][N:16]1[C:15]([C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]([CH3:36])([CH3:35])[C:25]=4[CH:24]=3)=[CH:7][CH:6]=2)[CH2:9][C:10]([OH:12])=[O:11])=[CH:19][N:18]=[N:17]1
Reactant: CCOC(=O)C[C@@H](c1ccc(O)cc1)c1cnnn1C
Reactant: CC1(C)CCC(C)(C)c2cc(CBr)ccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1nncc1[C@@H](CC(=O)O)c1ccc(OCc2ccc3c(c2)C(C)(C)CCC3(C)C)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 40 %

Procedure:
A mixture of 73.6 (0.15 mmol), 6-(bromomethyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene (0.18 mmol) and cesium carbonate (0.2 mmol) in DMF (2 mL), was stirred at room temperature for 16 hours. To the reaction mixture was added LiOH in water (1 mL, 1N solution), and the resulting mixture was stirred at 50° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 73 (26 mg, 0.06 mmol) after lyophilization. MS ESI (pos.) m/e 448.3 (M+H). 1H NMR (500 MHz) (CDCl3) δ 7.95 (1H, s), 7.71 (1H, s), 7.33-7.36 (2H, m), 7.20 (1H, dd, J=7.9, 1.5 Hz), 7.07 (2H, d, J=8.5 Hz), 6.97 (2H, d, J=8.9 Hz), 4.98 (2H, s), 4.51-4.55 (1H, m), 3.86 (3H, s), 3.11-3.17 (1 H, m), 3.01-3.07 (1H, m), 1.72 (4H, s), 1.31 (6H, s) 1.30 (6H, s).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C(OCC)(=O)C.[N:15]#[C:16]Br.[OH-]>O>[NH2:15][C:16]1[O:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=1
Reactant: Nc1ccccc1O
Reactant: N#CBr
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: Nc1nc2ccccc2o1
Temperature: 45 °C
Reaction time: 12 h
Yield: 88.2 %

Procedure:
A mixture of 2.5 g 2-aminophenol (6-1) and 20 ml ethyl acetate was heated to 45° C. 3 g of cyanogen bromide was added to the mixture. The mixture was stirred at 45-50° C. for 12 hours. After cooling to room temperature, 1.5 g of podium hydroxide in 15 ml of water was added. The organic layer was separated and washed with brine until neutral pH. Toluene (5 ml) was added and the solvent was removed to yield 2.71 g (88%) 2-aminobenzoxazol (6-2).
Reaction SMILES: [NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:10]([NH:12][C@H:13]([C:20](O)=[O:21])[CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:33][C@H:34]([C:39]([NH:41][C@H:42]([C:46]([NH:48][C@H:49]([C:54]([OH:56])=[O:55])[C@H:50]([CH2:52][CH3:53])[CH3:51])=[O:47])[CH:43]([CH3:45])[CH3:44])=[O:40])[CH2:35][CH:36]([CH3:38])[CH3:37].[C:57]([CH2:60][C:61]1[N:62]=[C:63]([NH-:66])[S:64][CH:65]=1)(=[O:59])[NH2:58].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>>[NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:10]([NH:12][C@H:13]([C:20]([NH:33][C@H:34]([C:39]([NH:41][C@H:42]([C:46]([NH:48][C@H:49]([C:54]([OH:56])=[O:55])[C@H:50]([CH2:52][CH3:53])[CH3:51])=[O:47])[CH:43]([CH3:44])[CH3:45])=[O:40])[CH2:35][CH:36]([CH3:37])[CH3:38])=[O:21])[CH2:14][C:15]1[N:19]=[CH:18][NH:17][CH:16]=1)=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:57]([CH2:60][C:61]1[N:62]=[C:63]([NH-:66])[S:64][CH:65]=1)(=[O:59])[NH2:58]
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)O)OCc1ccccc1
Reactant: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)C(C)C)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Agent: [NH-]c1nc(CC(N)=O)cs1
Product: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(C)C)C(=O)O

Procedure:
In a manner analogous to that described in Example 1, using as starting materials 81 mg of Z-Phe-His-OH, 69 mg of H-Leu-Val-Ile-4-(carbamoylmethyl)-2-thiazolyl amide, 28 mg of HOBt and 39 mg of DCCI, the title compound is obtained after flash chromatography (65 g of silica gel 60, 40-63 μm, eluant system B7). Rf (B7)=0.21.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[CH2:19][C@H:18]([CH3:20])[CH2:17][C@H:16]([CH3:21])[CH2:15]2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:22][CH2:23][C:24]([OH:26])=[O:25].[OH-].[Na+].Cl>CC(C)=O.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[CH2:19][C@H:18]([CH3:20])[CH2:17][C@H:16]([CH3:21])[CH2:15]2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([NH:22][CH2:23][C:24]([OH:26])=[O:25])=[O:5]
Reactant: NCC(=O)O
Reactant: C[C@@H]1C[C@H](C)CN(S(=O)(=O)c2ccc(Cl)c(C(=O)Cl)c2)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: C[C@@H]1C[C@H](C)CN(S(=O)(=O)c2ccc(Cl)c(C(=O)NCC(=O)O)c2)C1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
2-Chloro-5-(cis-3,5-dimethylpiperidinosulfonyl)benzoyl chloride (2.4 g.) and glycine (525 mg.) are dissolved in 30 ml. of water, 30 ml. of acetone and 14 ml. of 1N sodium hydroxide. After stirring at room temperature for about 25 minutes, the reaction mixture is acidified with concentrated hydrochloric acid. The precipitated material is recrystallized from acetone (25 ml.)-hexane (40 ml.) to yield the product, m.p. 189.5°-191.5° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=O)[CH:2]=1.[CH3:9][C@@H:10]1[CH2:15][NH:14][C@@H:13]([CH3:16])[CH2:12][N:11]1[C:17]1[CH:18]=[CH:19][C:20]2[N:21]([C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=2)[N:22]=1>>[CH3:9][C@@H:10]1[CH2:15][N:14]([CH2:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[C@@H:13]([CH3:16])[CH2:12][N:11]1[C:17]1[CH:18]=[CH:19][C:20]2[N:21]([C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=2)[N:22]=1
Reactant: C[C@@H]1CN[C@@H](C)CN1c1ccc2nnc(C(F)(F)F)n2n1
Reactant: O=Cc1cccnc1
Product: C[C@@H]1CN(Cc2cccnc2)[C@@H](C)CN1c1ccc2nnc(C(F)(F)F)n2n1
Yield: 84 %

Procedure:
A mixture of pyridine-3-carboxaldehyde and 6-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine was allowed to react by General Synthetic Method 5 to give 6-[(2R,5S)-2,5-dimethyl-4-(3-pyridylmethyl)piperazin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine in 84% yield.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[CH:7]=[CH:6][C:5]=1[O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]([F:36])([F:35])[F:34])=[CH:23][C:22]=1[N+:37]([O-])=O)([O-])=O.[H][H]>C(O)C.[Pt]=O>[NH2:37][C:22]1[CH:23]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]([F:35])([F:36])[F:34])[CH:25]=[CH:26][C:21]=1[O:20][C:5]1[CH:6]=[CH:7][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:17])([F:18])[F:19])=[CH:9][C:4]=1[NH2:1]
Reactant: [H][H]
Reactant: O=[N+]([O-])c1cc(-c2ccccc2C(F)(F)F)ccc1Oc1ccc(-c2ccccc2C(F)(F)F)cc1[N+](=O)[O-]
Agent: O=[Pt]
Solvent: CCO
Product: Nc1cc(-c2ccccc2C(F)(F)F)ccc1Oc1ccc(-c2ccccc2C(F)(F)F)cc1N
Yield: 49.3 %

Procedure:
2-Nitro-α,α,α-trifluoro-p-tolylphenyl ether (57.0 g., 0.209 mole) is dissolved in ethanol (200 ml.) and shaken in an atmosphere of hydrogen in a Parr apparatus in the presence of platinum oxide (100 mg.) until uptake is complete. The catalyst is removed by filtration and the solvent stripped off to give 2-amino-α,α,α-trifluoro-p-tolyl phenylether (50.3 g. 99%) which is used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:22]=3)=[CH:17][CH:16]=2)=[CH:11][C:10]([C:31]([F:34])([F:33])[F:32])=[N:9]1.CO.C=O.[C:39]([BH3-])#N.[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([CH2:13][N:14]([CH3:39])[C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([S:27]([CH3:30])(=[O:28])=[O:29])[CH:22]=3)=[CH:19][CH:20]=2)=[CH:11][C:10]([C:31]([F:34])([F:32])[F:33])=[N:9]1
Reactant: CS(=O)(=O)c1cccc(-c2ccc(NCc3cc(C(F)(F)F)nn3-c3ccccc3Cl)cc2)c1
Reactant: [BH3-]C#N
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CN(Cc1cc(C(F)(F)F)nn1-c1ccccc1Cl)c1ccc(-c2cccc(S(C)(=O)=O)c2)cc1

Procedure:
Into an 8 mL vial was weighed 215 mg of N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3′-(methylsulfonyl)biphenyl-4-amine (0.42 mmol). Addition of 2 mL of methanol followed by 0.5 mL of acetic acid, and 150 μL of 37% aqueous formaldehyde solution afforded a solution that was treated with 40 mg of sodium cyanoborohydride (0.64 mmol). After 30 min. at room temperature the reaction was quenched by the addition of 6N HCl (aq.). After gas evolution had subsided, the reaction mixture was diluted with EtOAc and the aqueous was made basic by the addition of saturated aqueous NaHCO3. The basic aqueous was extracted with EtOAc (3×) and the combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo to afford a colorless film. The crude product was purified by silica gel flash chromatography on a 12 g column using gradient elution from 0% to 100% EtOAc/hexane. Appropriate fractions were combined and concentrated in vacuo to afford N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-N-methyl-3′-(methylsulfonyl)biphenyl-4-amine as a colorless film. This material was impure by NMR analysis and was further purified by preparative reverse phase HPLC eluting with a gradient from 30% to 100% MeCN in H2O (each with 0.05% trifluoroacetic acid). The appropriate fractions were made basic by addition of saturated aqueous NaHCO3 solution and concentrated in vacuo to remove most of the acetonitrile. The resulting basic aqueous was extracted with CH2Cl2 (4×). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-N-methyl-3′-(methylsulfonyl)biphenyl-4-amine as a brittle foam that was broken up into a white powder, yield 126 mg (57% yield): 1H NMR (400 MHz, CDCl3): δ 8.11-8.08 (m, 1H, 7.84-7.79 (m, 2H, 7.62-7.56 (m, 2H, 7.52-7.40 (m, 5H), 6.72-6.67 (m, 2H), 6.52 (s, 1H), 4.43 (br s, 1H), 3.09 (s, 3H), 2.94 (S, 3H); MS (ESI) m/z 520.3 [M+H]+.
Reaction SMILES: [CH2:1]([N:13]1[N:17]=[N:16][C:15]([CH2:18][CH2:19][C:20]([OH:22])=O)=[N:14]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[F:23][C:24]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:25]=1[NH2:26]>>[F:23][C:24]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:25]=1[NH:26][C:20](=[O:22])[CH2:19][CH2:18][C:15]1[N:16]=[N:17][N:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[N:14]=1
Reactant: Nc1ccc(F)cc1F
Reactant: CCCCCCCCCCCCn1nnc(CCC(=O)O)n1
Product: CCCCCCCCCCCCn1nnc(CCC(=O)Nc2ccc(F)cc2F)n1

Procedure:
In a manner similar to Example 34, 2-dodecyl-2H-tetrazole-5-propanoic acid was condensed with 2,4-difluoroaniline to give the title compound, mp 86°-87° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]#[CH:18])=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.Br[C:20]1[CH:21]=[CH:22][C:23]([O:35][CH3:36])=[C:24]([S:26]([NH:29][C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])(=[O:28])=[O:27])[CH:25]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]#[C:18][C:20]4[CH:21]=[CH:22][C:23]([O:35][CH3:36])=[C:24]([S:26]([NH:29][C:30]([CH3:33])([CH3:34])[CH2:31][OH:32])(=[O:28])=[O:27])[CH:25]=4)=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: COc1ccc(Br)cc1S(=O)(=O)NC(C)(C)CO
Reactant: C#Cc1cnn2ccc(-c3ccc(Cl)cc3)nc12
Product: COc1ccc(C#Cc2cnn3ccc(-c4ccc(Cl)cc4)nc23)cc1S(=O)(=O)NC(C)(C)CO

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-3-ethynyl-pyrazolo[1,5-a]pyrimidine (example C.6) (63 mg, 0.25 mmol) and 5-bromo-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-benzenesulfonamide (85 mg, 0.25 mmol) according to general procedure II. Obtained as a yellow solid (52 mg, 41%). MS (ISP) 511.1 [(M+H)+]; mp 264–266° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][NH:17][C:18]([CH3:20])=[O:19])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[NH:21]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C@@H:22]([C:29](O)=[O:30])[CH2:23][CH2:24][S:25]([CH3:28])(=[O:27])=[O:26]>>[NH:21]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C@@H:22]([C:29]([NH:1][CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][NH:17][C:18]([CH3:20])=[O:19])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4])=[O:30])[CH2:23][CH2:24][S:25]([CH3:28])(=[O:26])=[O:27]
Reactant: CC(C)(C)OC(=O)N[C@H](CCS(C)(=O)=O)C(=O)O
Reactant: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CN
Product: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](CCS(C)(=O)=O)NC(=O)OC(C)(C)C
Yield: 52.7 %

Procedure:
Using H-Gly-Phe-NHNH-COCH3 (0.69 g) and BOC-(D)-Met(O2)-OH (0.66 g), the desired compound (0.67 g) is obtained in a similar manner to (III)of Example 45. m.p. 198°-199° C.(decomp.), [α]D23 -2.5°(c=0.49, DMF), Rf1 =0.25.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH:6]1[CH3:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:32]>>[Br:32][CH2:2][CH2:3][CH2:4][CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH:6]1[CH3:11]
Reactant: BrC(Br)(Br)Br
Reactant: CC1CC(=O)NC1CCCO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC1CC(=O)NC1CCCBr

Procedure:
A mixture of the title compound of EXAMPLE 235 is treated with triphenylphosphine and carbon tetrabromide by the method of EXAMPLE 224 to generate the title material.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH3:11])[CH:3]=1.[C:12]1([S:18]([N:21]2[C:25]3=[CH:26][N:27]=[CH:28][CH:29]=[C:24]3[C:23](I)=[CH:22]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[C:12]1([S:18]([N:21]2[C:25]3=[CH:26][N:27]=[CH:28][CH:29]=[C:24]3[C:23]([C:2]3[C:10]4[C:5](=[N:6][CH:7]=[CH:8][CH:9]=4)[N:4]([CH3:11])[CH:3]=3)=[CH:22]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Cn1cc(I)c2cccnc21
Reactant: O=S(=O)(c1ccccc1)n1cc(I)c2ccncc21
Product: Cn1cc(-c2cn(S(=O)(=O)c3ccccc3)c3cnccc23)c2cccnc21

Procedure:
Analogously to Example 5, 3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine is reacted with 1-benzenesulfonyl-3-iodo-1H-pyrrolo[2,3-c]pyridine to give 1-benzenesulfonyl-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo-[2,3-c]pyridine.
Reaction SMILES: [Cl:1][C:2]1[C:3](I)=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18]CC)=[O:17])=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].[CH2:28](B(CC)CC)[CH3:29]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([CH2:28][CH3:29])=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:13])([F:14])[F:15])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2
Reactant: CCOC(=O)C1=Cc2c(ccc(Cl)c2I)OC1C(F)(F)F
Reactant: CCB(CC)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCc1c(Cl)ccc2c1C=C(C(=O)O)C(C(F)(F)F)O2
Temperature: 110 °C

Procedure:
To the mixture of ethyl 6-chloro-5-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.3g, 0.7 mmol), potassium carbonate(109 mg, 2.87 mmol) and tetrakistriphenyl-palladium (0) (81 mg, 0.07 mmol) in 3 mL of anhydrous DMF was added triethylboron (1.0M/THF, 1.05 mL, 1.05 mmol) under nitrogen. The resulting mixture was heated to 110° C. for five hrs. The reaction was cooled to room temperature, and diluted with 100 mL of ethyl acetate. The resulting organic phase was washed with brine. After removing the solvent, the residue was dissolved in 3 mL of THF, followed by addition of a solution of lithium hydroxide hydrate in 3 mL of water. To the resulting mixture was further added 3 mL of ethanol. The resulting solution was then heated to 80° C. for three hrs. The volatiles were then removed. The residue was diluted with water, and acidified in an ice/water bath with dilute hydrochloric acid. The product was extracted with ethyl acetate. The organic extracts were washed with brine, and dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on short silica gel with 3:7 EtOAc/hexane+1% HOAc to remove the polar impurities. After concentrating the collected fraction, the residue was further purified on reverse phase HPLC. It gave 75 mg slightly yellow solid. M.P.=171.5-172.5° C. 1H NMR (CDCl3/400 Mz), 8.07(s, 1H), 7.32(d, J=8.8 Hz, 1H), 6.82(d, J=8.8 Hz, 1H), 5.65(q, J=6.8 Hz, 1H), 2.91(m, 2H), 1.18(t, J=7.6 Hz, 3H). 13C NMR(CDCl3/400 MHz) 169.5, 152.8, 141.5, 136.5, 134.1, 127.7, 123.4(q, J=287.7 Hz), 118.6, 116.3, 115.5, 69.8(q, J=33.4 Hz), 23.1, 14.7. 19F NMR(CDCl3/400 Mz) −78.72(d, J=6.8 Hz). MS(ES−)=305.0 (M−H, 100). High resolution MS(ES−), m/e calc. For C13H10ClF3O3: 305.0198 (M−H), found: 305.0157.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:11]([NH:12][C:13]2[CH:14]=[N:15][CH:16]=[N:17][CH:18]=2)=[CH:10][CH:9]=[C:8]([CH:19]2[CH2:21][CH2:20]2)[N:7]=1)=[O:5])C.[OH-].[Na+].Cl>CCO>[CH:19]1([C:8]2[N:7]=[C:6]([C:4]([OH:5])=[O:3])[C:11]([NH:12][C:13]3[CH:18]=[N:17][CH:16]=[N:15][CH:14]=3)=[CH:10][CH:9]=2)[CH2:20][CH2:21]1
Reactant: CCOC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1nc(C2CC2)ccc1Nc1cncnc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.4 %

Procedure:
A suspension of 6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carboxylic acid ethyl ester (1.85 g, 6.5 mmol) from example A-1 in EtOH (15 ml) was treated with 1N NaOH (13 ml). The reaction mixture was stirred at rt overnight. The compact suspension was brought to pH 6 by addition of 1N HCl. The solid was collected by filtration, washed with EtOH and dried to give the product (1.29 g, 77%) as off-white solid.
Reaction SMILES: [F:1][CH:2]([F:34])[O:3][C:4]1[C:12]2[C:11](=O)[N:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][C:15]=3[F:24])[CH:9]([OH:25])[C:8]=2[C:7]([O:26][CH:27]([F:29])[F:28])=[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=12.C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[F:34][CH:2]([F:1])[O:3][C:4]1[C:12]2[CH2:11][N:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][C:15]=3[F:24])[C:9](=[O:25])[C:8]=2[C:7]([O:26][CH:27]([F:28])[F:29])=[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=12
Reactant: O=C(O)Cc1ccc(N2C(=O)c3c(c(OC(F)F)c4ccccc4c3OC(F)F)C2O)c(F)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)Cc1ccc(N2Cc3c(c(OC(F)F)c4ccccc4c3OC(F)F)C2=O)c(F)c1
Reaction time: 0.08 h
Yield: 45.8 %

Procedure:
To a solution of (4-{4,9-bis[(difluoromethyl)oxy]-1-hydroxy-3-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl}-3-fluorophenyl)acetic acid (0.035 g, 0.072 mmol) in trifluoroacetic acid (2 ml) cooled to 0° C., was added triethylsilane (0.019 ml, 0.110 mmol). Stirring continued at 0° C. for 5 minutes and then the mixture was evaporated. The crude mixture was purified using MDAP. The clean fractions were evaporated to give the title compound (0.015 g, 0.033 mmol). LC/MS: Rt=3.15, [MH]+ 468.
Reaction SMILES: Cl.Br[CH:3]([F:15])[C:4](F)([F:13])[O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.[OH-].[Na+]>[Zn].C(O)(=O)C>[F:13][C:4]([O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1)=[CH:3][F:15]
Reactant: Nc1ccc(OC(F)(F)C(F)Br)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: Nc1ccc(OC(F)=CF)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 107.5 %

Procedure:
4.05 g (61.2 mmol) of zinc dust was added to a mixture of 5.0 g (16.3 mmol) of p-(2-bromo-1,1,2-trifluoroethoxy)benzeneamine hydrochloride 5 ml of 6N5HCl and 45 ml of glacial acetic acid. The mixture was stirred at room temperature for 31/2 hours, then poured into ice, made basic with 50 percent aqueous NaOH and extracted two times into ether. The combined ether layers were washed with dilute aqueous NaOH, washed with water, dried over MgSO4 and filtered. HCl gas was bubbled into the solution. The resulting white solid was collected by filtration to give 3.0 g (88 percent of theoretical) of the above-named aniline as the hydrochloride salt along with a 10 percent impurity of 4-(1,1,2-trifluoroethoxy)benzeneamine.
Reaction SMILES: [NH2:1][C:2]1[C:10]([N+:11]([O-])=O)=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[H][H]>CO.[Pd]>[NH2:11][C:10]1[C:2]([NH2:1])=[N:3][CH:4]=[C:5]([CH:9]=1)[C:6]([NH2:8])=[O:7]
Reactant: [H][H]
Reactant: NC(=O)c1cnc(N)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Product: NC(=O)c1cnc(N)c(N)c1

Procedure:
A suspension of 6-amino-5-nitronicotinamide (18 g, 99 mmol) and a cat. amount of Pd/C in methanol (600 ml) and the mixture was hydrogenated at room temperature and atmospheric pressure until the uptake of hydrogen ceased. Following filtration through celite, the methanol was evaporated under reduced pressure to give the title compound, 14.5 g (96%).
Reaction SMILES: C[Al](C)C.[NH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(N)C1C=CC=CC=1.[N:20]1([CH2:29][C:30]2[CH:40]=[CH:39][C:33]([C:34](OCC)=[O:35])=[CH:32][CH:31]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[CH:21]1>>[C:6]1([NH:5][C:34](=[O:35])[C:33]2[CH:32]=[CH:31][C:30]([CH2:29][N:20]3[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[N:22]=[CH:21]3)=[CH:40][CH:39]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCOC(=O)c1ccc(Cn2cnc3ccccc32)cc1
Reactant: Nc1ccccc1
Agent: C[Al](C)C
Solvent: NCc1ccccc1
Product: O=C(Nc1ccccc1)c1ccc(Cn2cnc3ccccc32)cc1
Yield: 13 %

Procedure:
Utilising a modification of the procedure described in Example 8 employing 4 equivalents of trimethylaluminium and 4 equivalents of aniline (0.67 g, 7.2 mmol) in lieu of benzylamine with respect to 1 equivalent of ethyl 4-(1H-benzimidazylmethyl)benzoate yielded a crude product was purified by column chromatography (flash silica gel, gradient elution 0-100% ethyl acetate in hexane) and recrystallised from methanol to give N-phenyl 4-(1H-benzimidazylmethyl)benzamide (75 mg, 13%) as a white crystalline solid.
Reaction SMILES: [CH2:1]([O:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]C)=[CH:21][CH:20]=2)=[N:17][CH:18]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(OC1C=NC(C2C=CC(CCCCCCCCCCCC)=CC=2)=NC=1)CCCCCCCCCC.C(OC1C=NC(C2C=CC(CCCCCCCCCCC)=CC=2)=NC=1)CCCCCCCCCC>>[CH2:1]([O:12][C:13]1[CH:14]=[N:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:21][CH:20]=2)=[N:17][CH:18]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCCCCCCCOc1cnc(-c2ccc(CCCCCC)cc2)nc1
Agent: CCCCCCCCCCCCc1ccc(-c2ncc(OCCCCCCCCCCC)cn2)cc1
Agent: CCCCCCCCCCCOc1cnc(-c2ccc(CCCCCCCCCCC)cc2)nc1
Product: CCCCCCCCCCCOc1cnc(-c2ccc(CCCCC)cc2)nc1

Procedure:
5-undecyloxy-2-(4-hexylphenyl)pyrimidine ##STR25## 5-undecyloxy-2-(4-heptylphenyl)pyrimidine ##STR26## 5-undecyloxy-2-(4-octylphenyl)pyrimidine ##STR27## 5-undecyloxy-2-(4-nonylphenyl)pyrimidine ##STR28## 5-undecyloxy-2-(4-decylphenyl)pyrimidine ##STR29## 5-undecyloxy-2-(4-undecylphenyl)pyrimidine 5-undecyloxy-2-(4-dodecylphenyl)pyrimidine