Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][CH2:12][CH2:13][OH:14].ClCCl.[CH3:18][S:19](Cl)(=[O:21])=[O:20]>C(N(CC)CC)C>[CH3:18][S:19]([O:14][CH2:13][CH2:12][O:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)(=[O:21])=[O:20]
Reactant: CS(=O)(=O)Cl
Reactant: OCCOc1ccc2ccccc2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCCOc1ccc2ccccc2c1

Procedure:
As described in Example 2, 13.5 g. of 2-(2-naphthyloxy)ethanol in 400 ml. of dichloromethane is reacted with 9.5 g. of methanesulfonyl chloride in the presence of 11.4 g. of triethylamine to give the product as tan crystals.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][C@H:11]2[C@H:13]([NH2:16])[CH2:14][CH2:15][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]1([C@H:23]([CH2:27][CH3:28])[C:24](O)=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:1]([N:8]1[CH2:12][C@@H:11]2[C@@H:13]([NH:16][C:24](=[O:25])[CH:23]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:27]3[CH2:28][CH2:4][CH2:3][CH2:2][CH2:1]3)[CH2:14][CH2:15][C@@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21
Reactant: CC[C@H](C(=O)O)c1ccccc1
Product: O=C(N[C@H]1CC[C@@H]2CN(Cc3ccccc3)C[C@@H]21)C(C1CCCCC1)C1CCCCC1

Procedure:
The title compound was prepared by substituting (3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine from Step A of Example 33 for (3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine and substituting 2,2-dicyclohexylacetic acid for (S)-2-phenylbutanoic acid in Step F of the procedure used to prepare Example 16: 1H NMR (400 MHz, CDCl3) δ ppm 7.32-7.27 (m, J=6.3, 4H), 7.24-7.18 (m, 1H), 5.22 (d, J=6.9, 1H), 4.11-3.99 (m, 1H), 3.62 (d, J=13.0, 1H), 3.46 (d, J=13.0, 1H), 2.67-2.58 (m, 2H), 2.54 (dd, J=4.2, 9.4, 1H), 2.51-2.43 (m, 1H), 2.31 (dt, J=4.0, 7.6, 1H), 2.25 (dd, J=4.2, 9.0, 1H), 2.08-1.99 (m, 1H), 1.87-1.76 (m, 1H), 1.67 (dd, J=15.7, 26.7, 10H), 1.55 (s, 3H), 1.50-1.38 (m, 2H), 1.31-1.02 (m, 8H), 1.00-0.85 (m, 2H); MS (ESI+) m/z 423 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([NH2:27])[CH:24]=[CH:25][CH:26]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[Cl:18][C:5]1[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)=[N:7][C:2]([NH:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([O:20][CH3:19])[CH:22]=2)=[N:3][CH:4]=1
Reactant: COc1cccc(N)c1
Reactant: COc1cccc(CNc2nc(Cl)ncc2Cl)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COc1cccc(CNc2nc(Nc3cccc(OC)c3)ncc2Cl)c1
Temperature: 105 °C
Yield: 34.7 %

Procedure:
Into a reaction flask were added 2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine (0.20 g, 0.70 mmol) (prepared according to Example 1, step A), 1,4-dioxane (20 mL), 3-methoxy-benzenamine (0.13 g, 1.0 mmol), and p-toluenesulfonic acid monohydrate (49 mg, 0.26 mmol). The mixture was heated at 105° C. for 2 days. To the mixture was added an aqueous solution of NaHCO3 (saturated, 0.5 mL) and the organic solvent was removed under vacuum. The aqueous layer was extracted with DCM twice. The combined organic layers were dried, filtered and concentrated. The crude product was purified by silica gel column chromatography to provide the desired product (90 mg, 30%). LCMS for C19H20ClN4O2 (M+H)+: m/z=371.1.
Reaction SMILES: [Br-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])C=CC=CC=1.CC(C)([O-])C.[K+].[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][C:43](=O)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34]>C1COCC1>[F:12][C:11]([F:14])([F:13])[CH2:10][CH:9]=[C:43]1[CH2:44][CH2:45][N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[CH2:41][CH2:42]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: FC(F)(F)CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(=CCC(F)(F)F)CC1
Reaction time: 0.25 h
Yield: 177.2 %

Procedure:
To a solution of triphenyl(3,3,3-trifluoropropyl)phosphanium bromide (Intermediate 213, 972 mg, 2 mmol) in THF (20 mL) at 0 C under nitrogen was added potassium tert-butoxide (235 mg, 2.1 mmol). The resulting reaction mixture was stirred at 0 C for 15 min and then a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (398 mg, 2 mmol) in THF (5 mL) was added. The solution was stirred for a further 1 h at 0 C and then evaporated to dryness. The resulting residue was dissolved in EtOAc (25 mL) and washed with water (2×25 mL). Combined organics were washed with brine, dried over magnesium sulfate and evaporated to dryness. The crude solid was dissolved in diethyl ether (50 mL) and then filtered to remove insoluble impurities. The filtrate was evaporated to dryness to afford tert-butyl 4-(3,3,3-trifluoropropylidene)piperidine-1-carboxylate (Intermediate 212, 0.99 g, triphenylphosphine detected as impurity) which was used without further purification.
Reaction SMILES: C(N(CC)CC)C.S([O-])([O-])(=O)=O.[Mg+2].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[NH2:23][CH:24]([CH2:29][CH2:30][CH2:31][CH3:32])[C:25]([O:27][CH3:28])=[O:26]>ClCCl>[CH:14](=[N:23][CH:24]([CH2:29][CH2:30][CH2:31][CH3:32])[C:25]([O:27][CH3:28])=[O:26])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CCCCC(N)C(=O)OC
Reactant: O=Cc1ccccc1
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCC(N=Cc1ccccc1)C(=O)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
Triethylamine (8.67 g) (supplied from Wako Pure Chemical Industries), 7.74 g of magnesium sulfate anhydrate and 4.55 g of benzaldehyde (supplied from Wako Pure Chemical Industries) were added to a suspension of 7.79 g of methyl 2-aminohexanoate hydrochloride (supplied from BACHEM) in 70 mL of dichloromethane, and stirred at room temperature overnight. The reaction suspension was filtrated and the filtrate was concentrated. Then 280 mL of ether was added to the residue. The resulting suspension was filtrated and the filtrate was concentrated. Again 280 mL of ether was added to the residue, and the filtration and the concentration were repeated in the same manner, to yield 10.0 g of the title compound.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]([C:20]#[C:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:16][C:17]([OH:19])=[O:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:28](O)[CH2:29][CH3:30]>OS(O)(=O)=O>[CH2:28]([O:18][C:17](=[O:19])[CH2:16][CH:15]([C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:8]=1)[C:20]#[C:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:29][CH3:30]
Reactant: CCCO
Reactant: COc1ccc(C(C#Cc2ccccc2)CC(=O)O)cc1OC1CCCC1
Agent: O=S(=O)(O)O
Product: CCCOC(=O)CC(C#Cc1ccccc1)c1ccc(OC)c(OC2CCCC2)c1

Procedure:
A solution of (+/-)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-phenylethynylpropionic acid (200 mg, 0.55 mmol) in n-propanol (15 ml) and conc. H2SO4 (1 drop) was heated at 95° for 5 hr. The solvents were evaporated, the residue taken up in Et2O, washed with H2O, aqueous K2CO3, dried and the solvent evaporated. The residue was purified by flash chromatography (alumina, neutral, activity 1, Et2O), and gave the titled compound as an oil, 125 mg (56%). 1H NMR (400 MHz, CDCl3) δ 7.40 (m, 2 H), 7.28 (m, 3 H), 6.98 (m, 2 H), 6.84 (d, 1 H), 4.80 (m, 1 H), 4.36 (t, 1 H), 4.06 (t, 2 H), 3.82 (s, 3 H), 2.90 (d of d, 1 H), 2.78 (d of d, 1 H), 1.78-1.96 (m, 6 H), 1.64 (m, 4 H), 0.90 (t, 3 H).
Reaction SMILES: C([Li])CCCCC.I[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[C:20]([CH:21]([CH3:23])[CH3:22])=[CH:19][C:18]([CH:24]([CH3:26])[CH3:25])=[CH:17][C:16]=1[CH:27]([CH3:29])[CH3:28].[P:30](Cl)([O:34]CC)[O:31][CH2:32][CH3:33].Cl>C1COCC1>[CH:21]([C:20]1[CH:19]=[C:18]([CH:24]([CH3:25])[CH3:26])[CH:17]=[C:16]([CH:27]([CH3:29])[CH3:28])[C:15]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[PH:30](=[O:34])[O:31][CH2:32][CH3:33])([CH3:22])[CH3:23]
Reactant: CC(C)c1cc(C(C)C)c(-c2ccccc2I)c(C(C)C)c1
Reactant: CCOP(Cl)OCC
Agent: Cl
Agent: [Li]CCCCCC
Solvent: C1CCOC1
Product: CCO[PH](=O)c1ccccc1-c1c(C(C)C)cc(C(C)C)cc1C(C)C
Temperature: -60 °C
Reaction time: 0.42 h
Yield: 94 %

Procedure:
A 1-L 3-neck round-bottom flask was fitted with an addition funnel and the atmosphere was purged with nitrogen. Anhydrous, degassed THF (170 ml) was added to the 1-L flask and cooled to −60° C. (internal temperature). The addition funnel was charged with hexyllithium (2.38 M in hexanes, 57 mL, 135 mmol, 2.0 equiv). The hexyllithium was transferred into the cold THF over 20 min, maintaining the temperature below −40° C. The solution was re-cooled to −60° C. (internal temperature). A solution of 2′-iodo-2,4,6-triisopropylbiphenyl (27.5 g, 67.7 mmol, 1.0 equiv) in 170 mL of anhydrous, degassed THF was transferred, via cannula, drop wise to the n-hexyllithium solution. This was done over 25 min while maintaining the temperature below −40° C. After addition, the reaction mixture was allowed to stir at −60° C. for 30 min. Diethyl chlorophosphite (19.62 mL, 135 mmol, 2.0 equiv) was added to the reaction mixture, over 10 min while maintaining the temperature below −40° C. After addition of diethyl chlorophosphite, the reaction was allowed to proceed at −60 ° C. for an additional 30 min. Aqueous hydrochloric acid (1 M, 338 mL, 338 mmol) was added at −60° C. The flask was removed from the cold bath and the reaction was allowed to warm to 22° C. The resultant solution was diluted with heptane (340 mL) and transferred to a separatory funnel. The layers were separated and the organic layer was assayed for product by quantitative HPLC (94% yield). The organic layer was concentrated under reduced pressure to give an oil which was used in the next reaction without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[O:9])=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18].CO.[BH4-].[Na+]>C(O)(=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[OH:9])=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18]
Reactant: Nc1ccc(C(=O)c2ccc(F)cc2)cc1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Nc1ccc(C(O)c2ccc(F)cc2)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99 %

Procedure:
To a stirred solution of 20 parts of (4-amino-3-nitrophenyl)(4-fluorophenyl)methanone in 120 parts of methanol were added 3.8 parts of sodium tetrahydroborate. The whole was stirred for 30 minutes at room temperature. 12 Parts of acetic acid were added and the mixture was stirred for 15 minutes. After evaporation, water was added to the residue. The product was extracted with 2,2'-oxybispropane. The extract was dried, filtered and evaporated, yielding 20 parts (99%) of 4-amino-α-(4-fluorophenyl)-3-nitrobenzenemethanol as a residue (int. 3).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[NH:5][C:6]1[N:11]=[C:10]([C:12]2[NH:16][C:15]([CH3:17])=[N:14][CH:13]=2)[CH:9]=[CH:8][N:7]=1.Cl[C:22]1C=C(NC(N)=N)C=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[NH:5][C:6]1[N:11]=[C:10]([C:12]2[N:16]([CH3:22])[C:15]([CH3:17])=[N:14][CH:13]=2)[CH:9]=[CH:8][N:7]=1
Reactant: Cc1ncc(-c2ccnc(Nc3cccc(Cl)c3)n2)[nH]1
Reactant: N=C(N)Nc1cccc(Cl)c1
Product: Cc1ncc(-c2ccnc(Nc3cccc(Cl)c3)n2)n1C
Yield: 29.3 %

Procedure:
5-(3-Dimethylaminoprop-2-en-1-oyl)-1,2-dimethylimidazole (Method 1; 111 mg, 0.58 mmol) and 3-chlorophenylguanidine (97 mg, 0.58 mmol) were treated as described in Example 1 to give the title compound 51 mg, (29%) as a solid. NMR: 2.40 (s, 3H), 3.97 (s, 3H), 6.98 (d, 1H), 7.15 (d, 1H), 7.30 (t, 1H), 7.58 (d, 1H), 7.67 (s, 1H), 7.97 (s, 1H), 8.40 (d, 1H), 9.68 (s, 1H); m/z: 300.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[S:10]([N:13]=C=O)(=[O:12])=[O:11].O.C(=O)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][S:10](=[O:12])(=[O:11])[NH2:13])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: O=C=NS(=O)(=O)Cl
Agent: O=C=O
Solvent: Cc1ccccc1
Solvent: O
Product: NS(=O)(=O)Oc1ccc(Cl)cc1
Temperature: 100 °C
Yield: 10.1 %

Procedure:
In one portion, 96 g (0.75 mole) of 4-chlorophenol was added to a stirred solution of 67.5 ml (0.75 mole) of chlorosulfonylisocyanate in 400 ml of toluene. The solution was heated at 100° C. for 16 hr and the solution chilled with an ice-acetone bath and water added dropwise until evolution of carbon dioxide ceased. The tan solid which precipitated from solution was collected and dried for 16 hr to yield 133.4 g. A 25 g portion was recrystallized from 100 ml of toluene to give 15.8 g of white solid, mp 103°-104° C.
Reaction SMILES: C(NC1C=CC([C:16]2[CH:24]=[C:23]3[C:19](C[N:21]([C@@H:26]([CH:31]([CH3:33])C)[C:27](OC)=[O:28])[C:22]3=[O:25])=[CH:18][CH:17]=2)=CC=1)(=O)C1C=CC=CC=1.[NH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:49]=[C:48]3[C:44]([CH2:45][N:46]([CH:51]4[CH2:56][CH2:55][CH2:54][CH:53]([C:57]([O:59][CH3:60])=[O:58])[CH2:52]4)[C:47]3=[O:50])=[CH:43][CH:42]=2)=[CH:37][CH:36]=1.CC1OC(C2C=CC=CC=2)=NC=1C(Cl)=O>>[CH3:33][C:31]1[O:25][C:22]([C:23]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:24]=2)=[N:21][C:26]=1[C:27]([NH:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]2[CH:49]=[C:48]3[C:44]([CH2:45][N:46]([CH:51]4[CH2:56][CH2:55][CH2:54][CH:53]([C:57]([O:59][CH3:60])=[O:58])[CH2:52]4)[C:47]3=[O:50])=[CH:43][CH:42]=2)=[CH:39][CH:40]=1)=[O:28]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Reactant: COC(=O)C1CCCC(N2Cc3ccc(-c4ccc(N)cc4)cc3C2=O)C1
Agent: Cc1oc(-c2ccccc2)nc1C(=O)Cl
Product: COC(=O)C1CCCC(N2Cc3ccc(-c4ccc(NC(=O)c5nc(-c6ccccc6)oc5C)cc4)cc3C2=O)C1
Yield: 65 %

Procedure:
The compound of example 552 was prepared analogous to compound of example 97 by reaction of compound of example 543 with 5-methyl-2-phenyloxazole-4-carbonyl chloride.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH:5]([N:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)[C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1.C([Li])CCC.CN(C)[CH:30]=[O:31].Cl>O1CCCC1.CCCCCC>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([CH:5]([N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:4]2[CH:20]=[CH:21][CH:22]=[C:2]([CH:30]=[O:31])[CH:3]=2)=[CH:7][CH:8]=1
Reactant: CN(C)C=O
Reactant: CN1CCN(C(c2ccc(Cl)cc2)c2cccc(Br)c2)CC1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CN1CCN(C(c2ccc(Cl)cc2)c2cccc(C=O)c2)CC1
Temperature: -78 °C

Procedure:
1-(3-Bromo-4'-chlorobenzhydryl)-4-methylpiperazine (see U.S. Pat. No. 4,757,074) (1.00 g, 2.63 mmole) was dissolved in 12 ml of dry tetrahydrofuran under nitrogen and cooled to -78° C. A solution of 1.1 M n-butyllithium in hexane (2.4 ml) was added dropwise and the reaction was stirred for ten minutes. N,N-Dimethylformamide (0.25 ml, 3.2 mmole) was added in one portion and the reaction was allowed to warm to -40° C. Hydrochloric acid (1.0 M, 20 ml) was added and the reaction was warmed to room temperature. The solution was washed with 20 ml of diethyl ether and the ethereal wash was discarded. The aqueous solution was made basic with aqueous sodium hydroxide and extracted with two 15 ml portions of chloroform. The combined chloroform extracts were dried over sodium sulfate and the solvent removed to give 738 mg of crude 1-(4-chloro-3'-formylbenzhydryl)-4-methylpiperazine as a dark oil.
Reaction SMILES: [CH2:1]([C:3]1([C:40]2[CH:45]=[CH:44][C:43]([OH:46])=[CH:42][CH:41]=2)[CH:12]([CH2:13]CCCCCCCCC(CCCCCCC(F)(F)C(F)(F)F)C(O)=O)[C:11]2[C:6](=[CH:7][C:8]([OH:39])=[CH:9][CH:10]=2)[O:5][CH2:4]1)[CH3:2].[F:47][C:48]([F:69])([C:65]([F:68])([F:67])[F:66])[CH2:49][CH2:50][CH2:51][CH:52]([CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH:63]=[CH2:64])[C:53]([O:55]CC)=[O:54]>>[CH2:1]([C:3]1([C:40]2[CH:41]=[CH:42][C:43]([OH:46])=[CH:44][CH:45]=2)[CH:12]([CH2:13][CH2:64][CH2:63][CH2:62][CH2:61][CH2:60][CH2:59][CH2:58][CH:52]([CH2:51][CH2:50][CH2:49][C:48]([F:47])([F:69])[C:65]([F:66])([F:67])[F:68])[C:53]([OH:55])=[O:54])[C:11]2[C:6](=[CH:7][C:8]([OH:39])=[CH:9][CH:10]=2)[O:5][CH2:4]1)[CH3:2]
Reactant: C=CCCCCCC(CCCC(F)(F)C(F)(F)F)C(=O)OCC
Reactant: CCC1(c2ccc(O)cc2)COc2cc(O)ccc2C1CCCCCCCCCC(CCCCCCC(F)(F)C(F)(F)F)C(=O)O
Product: CCC1(c2ccc(O)cc2)COc2cc(O)ccc2C1CCCCCCCCC(CCCC(F)(F)C(F)(F)F)C(=O)O

Procedure:
Starting with the allyl compound prepared in Example 21 and the ethyl 2-(4,4,5,5,5-pentafluoropentyl)-8-nonenoate prepared in Example 10, the same procedure as shown in Example 21 was repeated to give 10-[(3RS,4RS)-3-ethyl-7-hydroxy-3-(4-hydroxyphenyl)chroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)decanoic acid.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:10](O)[CH2:11][CH2:12][OH:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[O:13][CH2:12][CH2:11][CH2:10][O:5]1
Reactant: O=Cc1ccccc1Br
Reactant: OCCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: Brc1ccccc1C1OCCCO1

Procedure:
ortho-Bromobenzaldehyde (4a) (8 g, 43.24 mmol) was stirred with 1,3 propanediol (4.7 ml, 64.86 mmol) and p-toluenesulfonic acid monohydrate (164 mg, 0.86 mmol) in benzene (150 ml) in a flask equipped with a Dean-Stark trap and a condenser. The mixture was heated at reflux for 12 hrs, cooled, and extracted with 2 M NaOH (100 ml), and brine (100 ml×3). The solution was dried over MgSO4, and the solvent evaporated to the title compound in quantitative yield.
Reaction SMILES: C([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])[N:10]=[N:9]1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[NH:8]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])[N:10]=[N:9]1
Reactant: [H][H]
Reactant: O=C(O)CCc1cn(Cc2ccccc2)nn1
Agent: [Pd]
Solvent: CO
Product: O=C(O)CCc1c[nH]nn1
Temperature: 60 °C
Reaction time: 16 h
Yield: 66.6 %

Procedure:
39 mg of palladium-on-charcoal at 10% are added to a solution containing 390 mg (1.7 mmol) of 3-(1-benzyl-1H[1,2,3]triazol-4-yl)propanoic acid in 3 ml of methanol. The reaction mixture is placed under 10 bar of hydrogen pressure and stirred at 60° C. for 16 hours. After filtration through celite, the solvents are evaporated off and the residue is purified by silica gel chromatography (eluent 95/5 dichloro-methane/methanol). 159.8 mg of 3-(1H[1,2,3]triazol-4-yl)propanoic acid are obtained in the form of a white powder with a yield of 67%.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH2:10][NH:11][CH2:12][CH2:13][OH:14])[CH:3]=[CH:2]1.C(N(CC)CC)C.Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>ClCCCl>[CH2:26]([O:25][C:23](=[O:24])[N:11]([CH2:12][CH2:13][OH:14])[CH2:10][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[NH:1][CH:2]=[CH:3]2)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: OCCNCc1cccc2cc[nH]c12
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: O=C(OCc1ccccc1)N(CCO)Cc1cccc2cc[nH]c12
Temperature: 25 °C
Reaction time: 2 h
Yield: 37.2 %

Procedure:
To a solution of 2-[(1H-indol-7-ylmethyl)-amino]-ethanol (4.4 g) in 1,2-dichloroethane (40 mL) was added triethylamine (4.85 mL, 34.6 mmol) followed by benzyl chloroformate (3.57 mL, 25.34 mmol). The mixture was allowed to stir at room temperature for 2 hours. The mixture was quenched by addition of water (20 mL), and 1.0 M sodium hydroxide (10 mL). The organic layer was separated and the aqueous layer extracted with 1,2-dichloroethane (20 mL). The combined organic extracts were washed with 1.0 M hydrochloric acid (20 mL), water (20 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography, eluting with 20% ethyl acetate in hexanes to 40% ethyl acetate in hexanes to afford (2-hydroxy-ethyl)-(1H-indol-7-ylmethyl)-carbamic acid benzyl ester (2.79 g, 52% combined yield for two steps) as a colorless oil. 1H NMR (CDCl3) 400 MHz δ: 9.97 (br s, 1H), 7.75-6.9 (m, 8H), 6.54 (br s, 1H), 5.21 (s, 2H), 4.9-4.6 (m, 3H), 3.85-3.57 (m, 2H), 3.55-3.23 (m, 3H); LCMS M+H=325.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([C:14]2[C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=[CH:16][N:15]=2)=O)=[C:4]1[CH3:23])[CH3:2].[C:24]1([C:30]2[C:31]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:32][N:33]3[C:38]=2[CH:37]=[CH:36][CH:35]=[CH:34]3)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(OC(=O)C)(=O)C>C(Cl)(Cl)Cl>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2([C:32]3[N:33]4[C:38]([CH:37]=[CH:36][CH:35]=[CH:34]4)=[C:30]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:31]=3[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:19]3[C:20](=[O:21])[O:22]2)=[C:4]1[CH3:23])[CH3:2]
Reactant: CCn1c(C)c(C(=O)c2ncccc2C(=O)O)c2ccccc21
Reactant: c1ccc(-c2cn3ccccc3c2-c2ccccc2)cc1
Solvent: CC(=O)OC(C)=O
Solvent: ClC(Cl)Cl
Product: CCn1c(C)c(C2(c3c(-c4ccccc4)c(-c4ccccc4)c4ccccn34)OC(=O)c3cccnc32)c2ccccc21

Procedure:
A mixture of 1.6 grams of (1-ethyl-2-methylindol-3-yl) (3-carboxypyridin-2-yl)ketone, 1.85 grams of 1,2-diphenylindolizine and 10 ml. of acetic anhydride was heated at about 40° C. for 104 minutes and then cooled in an ice bath. The reaction mixture was filtered and the product was repeatedly recrystallized from a toluene-petroleum ether mixture until a constant melting point of 206.5°-207.5° C. was obtained. A chloroform solution of the final product produced a blue color when applied to a record sheet material coated with a zinc-modified phenolic resin.
Reaction SMILES: [Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][C:5]([C:6](Cl)=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1.[CH2:15]([N:17]([CH2:21][CH3:22])[CH2:18][CH2:19][NH2:20])[CH3:16].[OH-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][C:5]([C:6]([NH:20][CH2:19][CH2:18][N:17]([CH2:21][CH3:22])[CH2:15][CH3:16])=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1
Reactant: CCN(CC)CCN
Reactant: COc1cc(Cl)c(C#N)cc1C(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CCN(CC)CCNC(=O)c1cc(C#N)c(Cl)cc1OC

Procedure:
While stirring under nitrogen, at minus 30°, a solution of 23 g (0.1 mol) of 4-chloro-5-cyano-2-methoxybenzoic acid chloride in 70 ml of methylene chloride is added dropwise to a solution of 11.6 g (0.1 mol) of 2-diethylaminoethylamine in 100 ml of methylene chloride. The resulting white suspension is then stirred at room temperature for 15 hours, 105 ml (0.105 mol) of 1M sodium hydroxide solution are then added dropwise thereto and the whole is stirred until 2 distinct layers have formed and then separated in a separating funnel, and the aqueous phase is again extracted by shaking with 50 ml of methylene chloride. The combined organic phases are dried over magnesium sulphate and filtered, 150 ml of cyclohexane are added and methylene chloride is distilled off until the distillation temperature is 70°. After cooling, the base that has crystallised out is filtered off with suction and then washed with cyclohexane. After drying, 4-chloro-5-cyano-N-(2-diethylaminoethyl)- 2-methoxybenzamide having a melting point of 104°-105° is obtained.