Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:42]=[CH:41][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:33][CH:28]4[CH2:27]3)=[N:9]2)=[CH:5][CH:4]=1.[F:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]2[C:55](=[O:56])[C:54]([C:57](O)=[O:58])=[CH:53][CH:52]=[N:51]2)=[CH:46][CH:45]=1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:25][C:19]1[CH:20]=[C:21]([NH:24][C:57]([C:54]2[C:55](=[O:56])[N:50]([C:47]3[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=3)[N:51]=[CH:52][CH:53]=2)=[O:58])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:42][CH:41]=3)[N:9]=[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[CH2:33][CH:28]4[CH2:27]3)[C:11]=12
Reactant: COc1ccc(Cn2nc(N3CC4CN(C(=O)OC(C)(C)C)CC4C3)c3c(Oc4ccc(N)cc4F)ccnc32)cc1
Reactant: O=C(O)c1ccnn(-c2ccc(F)cc2)c1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccc(Cn2nc(N3CC4CN(C(=O)OC(C)(C)C)CC4C3)c3c(Oc4ccc(NC(=O)c5ccnn(-c6ccc(F)cc6)c5=O)cc4F)ccnc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.9 %

Procedure:
A round-bottomed flask was charged with tert-butyl 5-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (44.8 mg, 0.0780 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (54.8 mg, 0.234 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (74.7 mg, 0.390 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (52.7 mg, 0.390 mmol), N-ethyl-N-isopropylpropan-2-amine (101 mg, 0.780 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction was partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (42.5 mg, 68.9%). LRMS (APCI pos): m/e 691 (M−99).
Reaction SMILES: [C:1]([C:3]1[C:11]2[S:10][N:9]=[N:8][C:7]=2[CH:6]=[CH:5][CH:4]=1)#[N:2].[ClH:12].[CH2:13]([O:15]CC)[CH3:14]>C(O)C.O1CCCC1>[ClH:12].[S:10]1[C:11]2[C:3]([C:1](=[NH:2])[O:15][CH2:13][CH3:14])=[CH:4][CH:5]=[CH:6][C:7]=2[N:8]=[N:9]1
Reactant: N#Cc1cccc2nnsc12
Reactant: CCOCC
Agent: Cl
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=N)c1cccc2nnsc12
Reaction time: 24 h

Procedure:
7.2 g of 7-cyanobenzo-1,2,3-thiadiazole are dissolved at 45° C. in 60 ml of absolute ethanol and 20 ml of tetrahydrofuran, and the solution is cooled to 0° C. and saturated with gaseous hydrochloric acid in the course of 1 hour at 0° C. to 15° C., with the exclusion of moisture. The reaction mixture is then stored for 24 hours in the refrigerator, treated with 70 ml of absolute diethyl ether and allowed to stand for another 4 days in the refrigerator. The solid is then filtered off, washed with diethyl ether and dried. This gives 9.4 g of compound 5.2 in the form of beige crystals of m.p. 270°-272° C.
Reaction SMILES: [CH3:1][CH:2]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:3]([C:5]1[CH:6]=[C:7]([OH:12])[CH:8]=[C:9]([CH:11]=1)[OH:10])[CH3:4].[CH3:18][C:19]1([CH3:30])[CH2:23][C:22](=O)[CH:21]([C:25](OCC)=[O:26])[CH2:20]1.P(Cl)(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1>[OH:10][C:9]1[C:8]2[C:22]3[CH2:23][C:19]([CH3:30])([CH3:18])[CH2:20][C:21]=3[C:25](=[O:26])[O:12][C:7]=2[CH:6]=[C:5]([CH:3]([CH:2]([CH3:1])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH3:4])[CH:11]=1
Reactant: CCCCCC(C)C(C)c1cc(O)cc(O)c1
Reactant: CCOC(=O)C1CC(C)(C)CC1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: CCCCCC(C)C(C)c1cc(O)c2c3c(c(=O)oc2c1)CC(C)(C)C3
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To 13.5 g. of 5-(3-methyl-2-octyl)-resorcinol and 10.5 g. of 4,4-dimethyl-2-carboethoxycyclopentanone [Canadian J. of Chem. 47, 1982-1988 (1969)] in 59 ml. of benzene was added 4.3 ml. of phosphorous oxychloride with stirring and refluxing for 6 hours. After the red solution was allowed to stand at room temperature for 8 hours, it was added to an ice and sodium carbonate solution. The colorless mixture was extracted with ether, dried over magnesium sulfate and concentrated. The mixture was extracted with cold pentane and the pentane was discarded. The residue [9-hydroxy-7-(3-methyl-2-octyl)-2,2,-dimethyl-4-oxo-1,2,3,4-tetrahydrocyclopenta[c] [l]benzopyran] was obtained as a gummy solid.
Reaction SMILES: NC1C=CC(O[CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]C2)=CC=1.[CH2:22]([N:26]1[CH:30]=[C:29]([C:31]2[S:35][C:34]([C:36]([OH:38])=O)=[CH:33][CH:32]=2)[CH:28]=[N:27]1)[CH:23]([CH3:25])[CH3:24].C(OC([N:49]1CC(C(O)=O)C1)=O)C1C=CC=CC=1>>[CH2:22]([N:26]1[CH:30]=[C:29]([C:31]2[S:35][C:34]([C:36]([NH:49][C@H:7]3[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9]3)=[O:38])=[CH:33][CH:32]=2)[CH:28]=[N:27]1)[CH:23]([CH3:25])[CH3:24]
Reactant: CC(C)Cn1cc(-c2ccc(C(=O)O)s2)cn1
Reactant: O=C(O)C1CN(C(=O)OCc2ccccc2)C1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(N)cc2)CC1
Product: CC(C)Cn1cc(-c2ccc(C(=O)N[C@H]3CCN(C(=O)OC(C)(C)C)C3)s2)cn1

Procedure:
The title compound was prepared as described in Example 1A, substituting (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][C:9]([CH3:22])=[C:8]1[CH2:7][C:6](=[O:23])[CH2:5][CH2:4]2.[C:24]([O-:27])(=[O:26])[CH3:25]>CO.[Pd]>[C:24]([OH:27])(=[O:26])[CH3:25].[OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][C@@H:9]([CH3:22])[C@H:8]1[CH2:7][C:6](=[O:23])[CH2:5][CH2:4]2
Reactant: CC(=O)[O-]
Reactant: CC1=C2CC(=O)CC[C@]2(CO)[C@H]2CC[C@]3(C)C(=O)CC[C@H]3[C@@H]2C1
Agent: [Pd]
Solvent: CO
Product: CC(=O)O
Product: C[C@@H]1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(CO)CCC(=O)C[C@H]12
Reaction time: 0.5 h

Procedure:
A solution of 19-hydroxy-6-methyl-5-androstene-3,17-dione bis ethylenektal acetate in methanol is hydrogenated with a 10% palladium-on-charcoal catalyst at atmospheric pressure for a period of about 8 hours. After filtration of the catalyst, additional methanol and aqueous hydrochloric acid are added to the filtrate and the solution is heated to its reflux temperature. After about 30 minutes, the solution is poured onto water, and the solid which separates is filtered and air dried. Crystallization of this solid from an ether-hexane solution yields 19-hydroxy-6β-methyl-5α-androstane-3,17-dione acetate.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](Cl)=[N:9]2)=[CH:4][N:3]=1.[CH3:13][N:14]1[CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=[N:15]1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:17]3[CH:16]=[N:15][N:14]([CH3:13])[CH:18]=3)=[N:9]2)=[CH:4][N:3]=1
Reactant: Clc1ccc2cnc(Br)cc2n1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cn1cc(-c2ccc3cnc(Br)cc3n2)cn1
Temperature: 60 °C
Yield: 54.8 %

Procedure:
7-Bromo-2-chloro-1,6-naphthyridine (Preparation 61, 44.5 mg 0.183 mmole) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (53.4 mg 0.256 mmole) were stirred in THF (1 mL) and 2M aqueous sodium carbonate solution (0.35 mL) was added. Palladium(dppf)dichloride.dichloromethane complex (4.0 mg, 0.0049 mmole) was added and the reaction heated at 60° C. for 4.5 hours under nitrogen. The reaction was diluted with ethyl acetate (15 mL) and the solution was washed with brine (7 mL). The brine was backwashed with ethyl acetate (7 mL) and the combined organic layers were dried and concentrated in vacuo. The residue was purified using preparative TLC eluting with EtOAc to afford the title compound (29 mg, 54%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](Cl)=[O:8])[CH:2]=1.[NH2:10][C:11]1[CH:12]=[C:13]([NH:18][C:19](=[O:28])[C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)[CH:14]=[CH:15][C:16]=1[Cl:17]>>[Cl:17][C:16]1[CH:15]=[CH:14][C:13]([NH:18][C:19](=[O:28])[C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)=[CH:12][C:11]=1[NH:10][C:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[O:8]
Reactant: N#Cc1ccc(C(=O)Nc2ccc(Cl)c(N)c2)cc1
Reactant: O=C(Cl)c1cccnc1
Product: N#Cc1ccc(C(=O)Nc2ccc(Cl)c(NC(=O)c3cccnc3)c2)cc1
Yield: 67 %

Procedure:
Using an analogous procedure to that described in Example 2, pyridine-3-carbonyl chloride was reacted with N-(3-amino-4-chlorophenyl)-4-cyanobenzamide to give the title compound in 67% yield; NMR Spectrum: (DMSOd6) 7.57 (d, 1H), 7.59 (m, 1H), 7.73 (d, 1H), 8.01 (d, 2H), 8.10 (m, 3H), 8.34 (d, 1H), 8.79 (d, 1H), 9.15 (d, 1H), 10.33 (s, 1H), 10.66 (s, 1H); Mass Spectrum M+H+ 377.
Reaction SMILES: [OH:1][CH2:2][C:3]([CH2:7][OH:8])([CH2:5][OH:6])[CH3:4].CO[C:11]([CH3:13])=[CH2:12].S(=O)(=O)(O)O>CC(C)=O>[CH3:4][C:3]1([CH2:7][OH:8])[CH2:5][O:6][C:11]([CH3:13])([CH3:12])[O:1][CH2:2]1
Reactant: CC(CO)(CO)CO
Reactant: C=C(C)OC
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Product: CC1(CO)COC(C)(C)OC1
Reaction time: 1 h
Yield: 96.8 %

Procedure:
1,1,1-Tris(hydroxymethyl)ethane (120.2 g) and 2-methoxypropene (75.0 g) were suspended in acetone (300 ml). After adding one drop of cone, sulfuric acid at 0° C., the mixture was stirred for 1 hour and then at room temperature for additional 2 hours. After distilling off the acetone, a fraction obtained under reduced pressure (1.7 mmHg) at 70° C. was collected to give (1,4,4-trimethyl-3,5-dioxanyl)methan-1-ol (155.2 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]#[N:9])[N:5]([CH3:7])[CH:6]=1.[Si:10]([O:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:10]([O:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:2]2[CH:3]=[C:4]([C:8]#[N:9])[N:5]([CH3:7])[CH:6]=2)=[CH:20][CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: Cn1cc(Br)cc1C#N
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(N)cc1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: Cn1cc(Nc2ccc(O[Si](C)(C)C(C)(C)C)cc2)cc1C#N
Temperature: 80 °C
Reaction time: 1 h

Procedure:
Nitrogen is bubbled through a solution of 4-bromo-1-methyl-1H-pyrrole-2-carbonitrile (2.82 g, 15.2 mmol) and 4-[(tert-butyldimethylsilyl)oxy]aniline (4.08 g, 18.3 mmol) in toluene (55 mL) for 5 minutes. Sodium tert-butylate (2.92 g, 30.4 mmol), tris(dibenzylideneacetone)dipalladium(0) (556 mg, 0.6 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (255 mg, 0.6 mmol) are then added to the reaction mixture. The mixture is stirred for 1 hour at 80° C. under nitrogen. The suspension is then cooled to ambient temperature and filtered over Celite. The Celite cake is then rinsed with ethyl acetate. The filtrate is washed with water and then with brine. The organic phase is dried over magnesium sulphate, filtered and concentrated in vacuo. The product is purified twice by chromatography over silica gel (AcOEt/heptane gradient), and then by trituration in heptane to obtain the expected product in the form of a solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([NH2:17])[CH:16]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].CCN(CC)CC.[Cl:26][CH2:27][CH2:28][CH2:29][C:30](Cl)=[O:31]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([NH:17][C:30](=[O:31])[CH2:29][CH2:28][CH2:27][Cl:26])[CH:16]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8]
Reactant: COC(=O)c1cc(N)cc(C(=O)OC(C)(C)C)c1
Reactant: O=C(Cl)CCCCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1cc(NC(=O)CCCCl)cc(C(=O)OC(C)(C)C)c1
Temperature: 0 °C
Reaction time: 3 h
Yield: 93.7 %

Procedure:
A suspension of 5-amino-isophthalic acid 1-tert-butyl ester 3-methyl ester (D79) (3.4 g, 13.5 mmol, 1 equiv) in CH2Cl2 (25 ml) was treated with NEt3 (2.32 g, 23 mmol, 1.1 equiv) and cooled to 0° C. 4-chlorobutyryl chloride (1.6 g, 15.7 mmol, 1.1 equiv) was added dropwise and the resulting solution was stirred at 0° C. for 3 h then allowed to warm to room temperature and washed with 2N aqueous HCl solution, dried over MgSO4 and concentrated in vacuo. The residue was triturated with iso-hexane and Et2O to give 5-(4-chloro-butanoylamino)-isophthalic acid 1-tert-butyl ester 3-methyl ester (D80) (4.5 g, 94%) as a white solid.
Reaction SMILES: [N:1]1[CH:6]=[C:5]([C:7]([OH:9])=O)[CH:4]=[N:3][CH:2]=1.[CH2:10]([O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1)[CH3:11]>>[CH2:10]([O:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:7]([C:5]2[CH:4]=[N:3][CH:2]=[N:1][CH:6]=2)=[O:9])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1)[CH3:11]
Reactant: O=C(O)c1cncnc1
Reactant: CCOc1ccc(N)c([N+](=O)[O-])c1
Product: CCOc1ccc(NC(=O)c2cncnc2)c([N+](=O)[O-])c1

Procedure:
The title compound was prepared from pyrimidine-5-carboxylic acid and 4-ethoxy-2-nitroaniline as a yellow solid as described in Example 15. 1H NMR (CDCl3): 11.16 (s, 1H), 9.43 (s, 1H), 9.32 (s, 2H), 8.81 (d, J=9.3, 1H), 7.76 (d, J=3.0, 1H), 7.34-7.27 (m, 1H), 4.12 (q, J=6.9, 2H), 1.47 (t, J=6.9, 3H).
Reaction SMILES: C[C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13]Cl.[NH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:22]([OH:26])=[CH:21][CH:20]=[CH:19][C:18]=2[CH:17]=1.[H-].[Na+].[CH3:29]N(C)C=O>>[NH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[O:26][CH:13]([CH3:29])[C:3]2[N:4]=[C:5]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[O:6][CH:2]=2)[CH:17]=1
Reactant: Nc1ccc2c(O)cccc2c1
Reactant: CN(C)C=O
Reactant: Cc1oc(-c2ccccc2)nc1CCl
Agent: [H-]
Agent: [Na+]
Product: CC(Oc1cccc2cc(N)ccc12)c1coc(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
5-methyl-2-phenyl-4-Chloromethyloxazole (3.34 g) is added to a chilled mixture of 2-Amino-5-naphthol (2.55 g) and sodium hydride (0.65 g) in dimethylformamide (100 mL). Let stir overnight at room temperature. Concentrate in vacuo. Redilute with ethylacetate and absorb onto silica gel. Chromatograph (ethyl acetate/hexane) to give 2-amino-5-(methyl-2-phenyl-oxazol-4-ylmethoxy)naphthalene (1.59 g, 30%). Without further characterization this amine and triethylamine (0.67 mL) were dissolved in dichloromethane (75 mL). Cooled in an acetone and dry ice bath. Triflic anhydride (0.81 mL) was added and the mixture had warmed to room temperature overnight. Partition between water and ethyl acetate. Separate and dry with magnesium sulfate. Concentrate at rotovap, and triturate with ethyl acetate to provide the title compound (0.70 g, 30%) as a white solid, m.p. 192-194° C. 1H NMR (DMSO-d6, 400 MHz): δ 2.49 (s, 3H), 5.21 (s, 2H), 7.17 (d, 1H), 7.36 (d, 1H), 7.46-755 (m, 5H), 7.73 (s, 1H), 7.93-7.97 (m, 2H), 8.13 (d, 1H). MS [EI, m/z]: 462 [M]+. Anal. Calcd. for C22H17F3N2O4S 0.75(H2O): C, 55.52; H, 3.92; N, 5.89. Found: C, 55.62; H, 4.13; N, 5.45.
Reaction SMILES: C([NH:11][C@H:12]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(OCC1C=CC=CC=1)=O.[H][H]>C(O)C.C(OCC)(=O)C.[Pd]>[NH2:11][C@H:12]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)[C@H](CCc1ccccc1)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)(C)OC(=O)[C@@H](N)CCc1ccccc1

Procedure:
A solution of (N-carbobenzyloxy)-(L)-homophenylalanine, tert-butyl ester (100 mg, 0.281 mmol) in anhydrous ethanol (2 mL) and anhydrous ethyl acetate (2 mL) was degassed and the reaction flask filled with hydrogen. 10% Palladium on carbon catalyst (25 mg) was added and the mixture was hydrogenated under a balloon of hydrogen at room temperature for 2.3 hr. The catalyst was removed by filtration through a pad of celite, and solvent was removed from the filtrate by rotoevaporation. After pumping under reduced pressure at room temperature, the material thus obtained (homogeneous by TLC in 4/1 hexane/ethyl acetate) was used in the subsequent reaction without further purification.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:22])[O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][CH2:17][CH2:16]3)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].FC(F)(F)S(O[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Si](C)(C)C)(=O)=O.[F-].[Cs+]>C(#N)C.C(OCC)(=O)C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:22])[O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:17][CH2:16]3)=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1ccc(NC(=O)Oc2ccc3c(c2)CCN3)cc1
Reactant: C[Si](C)(C)c1ccccc1OS(=O)(=O)C(F)(F)F
Agent: [Cs+]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(C)c1ccc(NC(=O)Oc2ccc3c(c2)CCN3c2ccccc2)cc1
Reaction time: 8 h
Yield: 8.2 %

Procedure:
To a solution of indolin-5-yl 4-isopropylphenylcarbamate (50 mg, 0.17 mmol) in 3.4 mL of acetonitrile was added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (41 μL, 0.17 mmol) and caesium fluoride (51 mg, 0.34 mmol) at room temperature, successively. After the reaction mixture was stirred at the same temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20) to obtain the title compound as a white solid (5.2 mg, 8%).
Reaction SMILES: [OH-:1].[Na+].C(Cl)Cl.[C:6](Cl)(Cl)=[O:7].[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>O>[C:6](=[O:7])([O:1][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[O:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: [OH-]
Reactant: O=C(Cl)Cl
Reactant: Oc1ccccc1
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: O=C(Oc1ccccc1)Oc1ccccc1
Temperature: 33 °C
Yield: 99.9 %

Procedure:
In a vertically upright cooled tubular reactor, a mixture of 145.2 kg/h of 14.5% strength sodium hydroxide solution produced by diluting 65.8 kg/h of a 32% strength sodium hydroxide solution with 79.4 kg/h of demineralized water, and 48.3 kg/h of phenol was continuously combined with a solution of 86.2 kg/h of methylene chloride and 27.5 kg/h of phosgene (8 mol % excess based on phenol). This reaction mixture was cooled to a temperature of 33° C. and after a median residence time of 15 seconds, a pH of 11.5 was measured. Then, in the second stage of the process, to this reaction mixture was added 5.4 kg/h of 50% strength NaOH, so that the pH of the second reaction stage, after a further residence time of 5 minutes, was 8.5. In the continuously operated reaction, metering fluctuations which occurred were contained by respective adaptations of the NaOH feeds. In the second stage of the process, the reaction mixture was constantly mixed by passing it through a tube provided with constrictions. The reaction temperature, after repeated addition of NaOH, was set to 30° C. by cooling. After separating off the organic phase from the aqueous phase (reaction wastewater), the DPC solution was washed with 0.6% strength hydrochloric acid and water. After removal of the solvent, 99.9% pure diphenyl carbonate was obtained. The reaction wastewater was combined with the wash phases and freed from solvent residues and catalyst by stripping with steam. After neutralization with hydrochloric acid and treatment with activated carbon, the reaction wastewater contained 17% by weight NaCl and less than 2 ppm of phenol.
Reaction SMILES: [F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]([CH2:14][CH2:15][N:16]([CH3:21])[CH2:17][CH2:18][CH2:19][NH2:20])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[C:24](N1C=CN=C1)(N1C=CN=C1)=[O:25].[CH3:36][N:37]([CH2:39][C:40]1[O:49][C:43]([CH2:44][S:45][CH2:46][CH2:47][NH2:48])=[CH:42][CH:41]=1)[CH3:38]>>[CH3:38][N:37]([CH2:39][C:40]1[O:49][C:43]([CH2:44][S:45][CH2:46][CH2:47][NH:48][C:24]([NH:20][CH2:19][CH2:18][CH2:17][N:16]([CH2:15][CH2:14][N:7]([CH2:6][C:5]2[CH:22]=[CH:23][C:2]([F:1])=[CH:3][CH:4]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH3:21])=[O:25])=[CH:42][CH:41]=1)[CH3:36]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CN(CCCN)CCN(Cc1ccc(F)cc1)c1ccccn1
Reactant: CN(C)Cc1ccc(CSCCN)o1
Product: CN(C)Cc1ccc(CSCCNC(=O)NCCCN(C)CCN(Cc2ccc(F)cc2)c2ccccn2)o1

Procedure:
Preparation is effected analogously to Example 63, using 0.57 g (1.8 mmol) of N-[2-[N-(4-fluorobenzyl)-N-(2-pyridyl)amino]ethyl]-N-methyl-1,3-propanediamine and the equimolar amounts of 1,1'-carbonyldiimidazole and 2-[[5-[(dimethylamino)methyl]furfuryl]thio]ethylamine as starting materials. Working up by chromatography analogously to Example 1 yields the purified title compound in the form of a viscous oil; MS(+FAB method): m/z (rel. int. [%])=557 ([M+H]+, 1), 109 (100); IR (KBr): 1600 cm-1 (C=O). For further analysis, a portion of the compound is converted into the O,O'-ditoluoyltartaric acid salt in an ethanol/ether solvent mixture; m.p.: 102° C. (ethanol/ether).
Reaction SMILES: [Cl-].C[O:3][C:4]([C@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][NH2+:7]1)=O.C(OCC)(=O)C.[OH-].[Na+].[NH3:20]>>[NH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][C@@H:6]1[C:4]([NH2:20])=[O:3]
Reactant: COC(=O)[C@H]1CCCC[NH2+]1
Reactant: N
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: NC(=O)[C@H]1CCCCN1
Temperature: 60 °C

Procedure:
(2R)-2-(Methoxycarbonyl)piperidinium chloride (2.6 g, 14.5 mmol) was dissolved in ammonia (0.88M, 30 ml). The reaction mixture was heated at 60° C. for 1.5 hr. The mixture was partitioned between ethyl acetate (100 ml) and sodium hydroxide (1N, 100 ml, 100 mmol), the aqueous was washed with ethyl acetate (3×100 ml). The combined organic layers were dried over sodium sulphate and the solvent evaporated under reduced pressure. Aqueous layer was acidified with hydrochloric acid and evaporated to dryness under reduced pressure. The resultant white solid was triturated with dichloromethane:methanol (9:1), the remaining solid was removed by filtration and the filtrate evaporated under reduced pressure to afford the title compound as a white solid, 1.14 g, (61%). LRMS: m/z=129 (MH+).