Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@@H:7]([CH3:12])[C:8]([O:10]C)=[O:9])=[C:4]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH2:25][CH3:26])(=[O:24])=[O:23])=[CH:18][C:17]=2[Cl:27])[CH:3]=1.[OH-].[Li+]>O.C1COCC1>[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@@H:7]([CH3:12])[C:8]([OH:10])=[O:9])=[C:4]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH2:25][CH3:26])(=[O:23])=[O:24])=[CH:18][C:17]=2[Cl:27])[CH:3]=1
Reactant: CCS(=O)(=O)c1ccc(Oc2cc(Cl)ccc2O[C@@H](C)C(=O)OC)c(Cl)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCS(=O)(=O)c1ccc(Oc2cc(Cl)ccc2O[C@@H](C)C(=O)O)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of the product from step (iii) (2.3 g) and lithium hydroxide (0.303 g) in water (10 ml) and THF (10 ml) was stirred at RT for 1 h. The mixture was diluted with water, extracted with diethylether then the aqueous layer acidified by 2M hydrochloric acid and extracted with ethylacetate. The ethyl acetate layer was dried, evaporated under reduced pressure and the residue purified by RPHPLC.
Reaction SMILES: [F:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:10])[CH2:8][OH:9])[C@H:4]([C:11]#[N:12])[CH2:3]1.C(N(CC)CC)C.Cl.CN(C)C.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>O.C(#N)C>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([O:9][CH2:8][C:7]([N:5]2[CH2:6][C@@H:2]([F:1])[CH2:3][C@H:4]2[C:11]#[N:12])=[O:10])(=[O:34])=[O:33])=[CH:28][CH:27]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: N#C[C@@H]1C[C@H](F)CN1C(=O)CO
Agent: CN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: N#C[C@@H]1C[C@H](F)CN1C(=O)COS(=O)(=O)c1ccc(Cl)cc1
Reaction time: 1 h
Yield: 49.1 %

Procedure:
(2S,4S)-4-fluoro-1-(2-hydroxyacetyl)pyrrolidine-2-carboni trile (259 mg), triethylamine (0.42 mL), trimethylamine hydrochloride (143 mg) and acetonitrile (5 mL) were mixed together. While this mixture was cooled in a salt-ice bath, 4-chlorobenzenesulfonyl chloride (350 mg) was added in portions and the mixture was further stirred for 1 hour. Subsequently, water (5 mL) was added and the mixture was extracted with ethyl acetate (2×30 mL). The ethyl acetate extracts were combined, washed with saturated brine (2×5 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=ethyl acetate) to give (2S,4S)-1-[2-[(4-chlorophenyl)sulfonyloxy]acetyl]-4-fluoropyrr olidine-2-carbonitrile as a white solid (256 mg, 49% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[C:11]=1[O:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[Cl:21])[C:5]([O:7][CH3:8])=[O:6].[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>N1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:21][C:14]1[CH:15]=[CH:16][C:17]([O:19][CH3:20])=[CH:18][C:13]=1[O:12][C:11]1[C:10]([O:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[NH:1][S:40]([C:37]1[CH:36]=[CH:35][C:34]([O:33][CH3:32])=[CH:39][CH:38]=1)(=[O:42])=[O:41]
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)c1cc(N)c(Oc2cc(OC)ccc2Cl)c(OCCOC2CCCCO2)c1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: COC(=O)c1cc(NS(=O)(=O)c2ccc(OC)cc2)c(Oc2cc(OC)ccc2Cl)c(OCCOC2CCCCO2)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
135 mg of methyl 3-amino-4-(2-chloro-5-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate were dissolved in pyridine (3 ml), treated while cooling with ice with a solution of 111 mg of 4-methoxy-benzenesulphonyl chloride in toluene (1 ml) and subsequently stirred at RT for 20 hours. The reaction mixture was poured on to ice/3M HCl, the product was extracted with ethyl acetate and the organic phase was washed with water and dried over magnesium sulphate. After removing the solvent there was obtained methyl 4-(2-chloro-5-methoxy-phenoxy)-3-(4-methoxy-benzenesulphonylamino)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate as a foam.
Reaction SMILES: [C:1]1([CH3:52])[CH:6]=[CH:5][C:4]([S:7]([NH:10][CH2:11][CH2:12][CH2:13][N:14]([S:42]([C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=2)(=[O:44])=[O:43])[CH2:15][CH2:16][N:17]([S:32]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)(=[O:34])=[O:33])[CH2:18]CCNS(C2C=CC(C)=CC=2)(=O)=O)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[H-].[Na+]>CN(C=O)C>[C:38]1([CH3:41])[CH:37]=[CH:36][C:35]([S:32]([N:17]2[CH2:18][N:17]([S:32]([C:35]3[CH:36]=[CH:37][C:38]([CH3:41])=[CH:39][CH:40]=3)(=[O:34])=[O:33])[CH2:16][CH2:15][N:14]([S:42]([C:45]3[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=3)(=[O:44])=[O:43])[CH2:13][CH2:12][CH2:11][N:10]([S:7]([C:4]3[CH:5]=[CH:6][C:1]([CH3:52])=[CH:2][CH:3]=3)(=[O:8])=[O:9])[CH2:12][CH2:13][N:14]([S:42]([C:45]3[CH:46]=[CH:47][C:48]([CH3:51])=[CH:49][CH:50]=3)(=[O:44])=[O:43])[CH2:15][CH2:16]2)(=[O:33])=[O:34])=[CH:40][CH:39]=1
Reactant: Cc1ccc(S(=O)(=O)NCCCN(CCN(CCCNS(=O)(=O)c2ccc(C)cc2)S(=O)(=O)c2ccc(C)cc2)S(=O)(=O)c2ccc(C)cc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N2CCCN(S(=O)(=O)c3ccc(C)cc3)CCN(S(=O)(=O)c3ccc(C)cc3)CN(S(=O)(=O)c3ccc(C)cc3)CCN(S(=O)(=O)c3ccc(C)cc3)CC2)cc1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 55 %

Procedure:
To a stirred solution of 1,5,8,12-tetra(p-toluenesulfonyl)-1,5,8,12-tetraazadodecane prepared as in Example 11A (36.9 g, 0.0467 mole) in anhydrous DMF (470 ml) was added sodium hydride (2.80 g--80% in mineral oil, 0.0933 mole) in portions under a dry nitrogen blanket. The resulting mixture was stirred for 30 minutes under a dry argon atmosphere. The solution was then heated to 100° C. and a solution of 3-(p-toluenesulfonyl)-3-azapentane-1,5-di-p-toluenesulfonate prepared as in Example 11B (26.5 g, 0.0467 mole) in anhydrous DMF (230 mole) was added dropwise over a 3 h period, maintaining the temperature at 100° C. After stirring the solution an additional 1 h at 100° C., the mixture was concentrated in vacuo to a volume of 400 ml. H2O (1.5 l) was slowly added at room temperature to crystallize the product. The resulting pale yellow solid was filtered, washed thoroughly with H2O and dried in vacuo. The crude product was purified by recrystallization from CH2Cl2 -hexane to give 26.3 g (55% yield) of the product as a white crystalline solid: mp 235.5-6.5° C. (dec.); 1H NMR (CDCl3) δ 2.09 (quint, J=6.6 Hz, 4 H), 2.44 (s, 6 H), 2.45 (s, 6 H), 2.46 (s, 3 H), 3.04 (t, J=7.5 Hz, 4 H), 3.13 (t, J=7.1 Hz, 4 H), 3.23 (m, 8 H), 3.45 (m, 4 H), 7.33 (m, 10 H), 7.72 (m, 10 H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([Br:8])=[CH:6][C:5]([CH2:9][C@@H:10]([NH:24]C(OC(C)(C)C)=O)[CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)=[CH:4][C:3]=1[Br:32].FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:24][C@H:10]([CH2:9][C:5]1[CH:6]=[C:7]([Br:8])[C:2]([NH2:1])=[C:3]([Br:32])[CH:4]=1)[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:14][CH2:13]1
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1cc(Br)c(N)c(Br)c1)CN1CCC(N2CCCCC2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1c(Br)cc(C[C@@H](N)CN2CCC(N3CCCCC3)CC2)cc1Br
Temperature: 10 °C

Procedure:
To a mixture of 4 g (7 mmol) of (R)-1-[3-(4-amino-3,5-dibromophenyl)-2-[N-[(1,1-dimethylethoxy)carbonyl]-amino]propyl]-4-(1-piperidinyl)-piperidine and 100 ml of methylene chloride, 40 ml of trifluoroacetic acid were slowly added dropwise, with stirring, at 10° C. The reaction mixture was stirred for 2 hours at room temperature and then evaporated down in vacuo. The residue was mixed with ice water, made basic by the addition of concentrated aqueous ammonia solution and extracted three times with 200 ml of diethylether. The combined ether extracts were dried and evaporated down in vacuo. 3.4 g (100% of theory) of an amorphous solid were obtained.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[B:32](OC)([O:35]C)[O:33]C.Cl>O1CCCC1>[CH2:20]([O:19][C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:11]=[CH:12][C:7]([B:32]([OH:35])[OH:33])=[CH:8][CH:9]=2)=[CH:14][CH:15]=1)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: COB(OC)OC
Reactant: CCCCCCCCCCCCOc1ccc(-c2ccc(Br)cc2)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCCCCCCCOc1ccc(-c2ccc(B(O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 22.9 %

Procedure:
Butyllithium (6 ml, 1.6 M in hexanes, 9.6 mmol) was added dropwise to a solution of 4-bromo-4′-(dodecyloxy)biphenyl (4 g, 9.6 mmol) in THF (tetrahydrofuran) (150 mL) under N2 at −78° C. with stirring. Stirring was continued for 1 h and trimethyl borate (3 g, 28.8 mmol) was added. The resulting mixture was warmed to room temperature overnight, acidified with HCl (2 M, 100 mL), extracted with EtOAc (3×200 ml), dried (MgSO4) and the solvent removed under reduced pressure. The residue was filtered through a short plug of silica using EtOAc (0-100% gradient in DCM) as eluent. The solvent was removed under reduced pressure and the residue washed with hexane to give the title compound (0.84 g, 23%) as a colourless powder.
Reaction SMILES: C[Al](C)C.[NH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.C[O:12][C:13](=O)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[C:37]4[C:32](=[C:33]([Cl:38])[CH:34]=[CH:35][CH:36]=4)[N:31]=[N:30][C:29]=3[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:23]=2)[CH:15]=1>C1(C)C=CC=CC=1>[Cl:38][C:33]1[CH:34]=[CH:35][CH:36]=[C:37]2[C:32]=1[N:31]=[N:30][C:29]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[C:28]2[C:24]1[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH2:20][C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([C:13]([N:5]3[CH2:10][CH2:9][O:8][CH2:7][CH2:6]3)=[O:12])[CH:15]=2)[CH:23]=1
Reactant: C1COCCN1
Reactant: COC(=O)c1cccc(COc2cccc(-c3c(-c4ccccc4)nnc4c(Cl)cccc34)c2)c1
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: O=C(c1cccc(COc2cccc(-c3c(-c4ccccc4)nnc4c(Cl)cccc34)c2)c1)N1CCOCC1
Temperature: 60 °C

Procedure:
A solution of trimethylaluminum (2 M solution in dichloromethane, 0.5 M) was added to a solution of morpholine (0.1 g) in 5 mL of toluene at room temperature. After 30 minutes 3-[3-(8-chloro-3-phenyl-cinnolin-4-yl)-phenoxymethyl]-benzoic acid methyl ester (50 mg) in 2 mL of toluene was added and the solution was heated to 60° C. for 15 hours. The reaction mixture was cooled to room temperature, quenched with diluted HCl and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by semi-preparative HPLC. MS (ES) m/z 536.2.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21](OS(C)(=O)=O)[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:28]=[N+:29]=[N-:30].[Na+]>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@H:21]([N:28]=[N+:29]=[N-:30])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: C[C@H](OS(C)(=O)=O)[C@@H]1[C@@H](O[Si](C)(C)C(C)(C)C)CCN1C(=O)OC(C)(C)C
Agent: [Na+]
Solvent: CCOC(C)=O
Product: C[C@@H](N=[N+]=[N-])[C@@H]1[C@@H](O[Si](C)(C)C(C)(C)C)CCN1C(=O)OC(C)(C)C
Temperature: 80 °C
Yield: 72.3 %

Procedure:
A mixture of 80B (650 mg, 1.53 mmol) and sodium azide (597 mg, 9,18 mmol) was heated at 80° C. for 2 days. The reaction was diluted with EtOAc (200 mL), washed with brine:water (1:1, 4×15 mL), dried (MgSO4), filtered and concentrated to give the crude product. Purification by chromatography (40 g ISCO silica gel cartridge, 0-20% EtOAc/hexane) provided 80C as a colorless oil (410 mg). MS (ES) m/z 271 [M−Boc+H]+.
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]([C:6](=[O:12])[NH:7][CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[CH:25]([NH2:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[CH:25]([NH:32][C:9]([CH2:8][NH:7][C:6](=[O:12])[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:14][CH:13]=1)=[O:11])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(O)CNC(=O)c1ccc(F)cc1
Reactant: NC(c1ccccc1)c1cc([N+](=O)[O-])ccc1Cl
Product: O=C(CNC(=O)c1ccc(F)cc1)NC(c1ccccc1)c1cc([N+](=O)[O-])ccc1Cl

Procedure:
Prepared in analogy to example 1.1 from 4-fluoro-hippuric acid (CA [366-79-0]) and rac-C-(2-chloro-5-nitro-phenyl)-C-phenyl-methylamine (example 4.4).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]([CH3:17])[C:6](=[O:16])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1>C(OCC)(=O)C.[Pt](=O)=O>[NH2:13][C:9]1[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=1)[C:6]([N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH3:17])=[O:16]
Reactant: COCCN(C)C(=O)c1cccc([N+](=O)[O-])c1
Agent: O=[Pt]=O
Solvent: CCOC(C)=O
Product: COCCN(C)C(=O)c1cccc(N)c1
Reaction time: 8 h
Yield: 103.6 %

Procedure:
To a stirred solution of N-(2-methoxyethyl)-N-methyl-3-nitrobenzamide (840 mg) in ethyl acetate (8 ml) was added platinum dioxide (160 mg) and the resulting heterogeneous mixture was stirred under hydrogen atmosphere for 8 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate to give 3-amino-N-(2-methoxyethyl)-N-methylbenzamide (761 mg) as a brown viscous oil.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2)([O-:3])=[O:2].[CH3:14]I.[BH4-].[Na+]>>[CH3:14][N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[CH:13][C:4]=2[N+:1]([O-:3])=[O:2])[CH2:9]1
Reactant: O=[N+]([O-])c1cccc2cnccc12
Reactant: CI
Agent: [BH4-]
Agent: [Na+]
Product: CN1CCc2c(cccc2[N+](=O)[O-])C1

Procedure:
5-Nitroisoquinoline was quaternized with methyl iodide and then reduced using sodium borohydride according to the procedures of Preparations 1 and 2 to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]3[N:14]=[C:15]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)=[CH:20][CH:19]=4)[N:16]=[C:12]3[CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:32]1([N:38]=[C:39]=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)(Cl)Cl>[C:32]1([NH:38][C:39]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:13]4[N:14]=[C:15]([NH:17][C:18]5[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]6[CH2:28][CH2:29][CH2:30][CH2:31]6)=[CH:20][CH:19]=5)[N:16]=[C:12]4[CH:11]=[CH:10][CH:9]=3)[CH:3]=2)=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: O=C=Nc1ccccc1
Reactant: Nc1cccc(-c2cccc3nc(Nc4ccc(OCCN5CCCC5)cc4)nn23)c1
Solvent: ClC(Cl)Cl
Product: O=C(Nc1ccccc1)Nc1cccc(-c2cccc3nc(Nc4ccc(OCCN5CCCC5)cc4)nn23)c1
Reaction time: 8 h

Procedure:
[5-(3-Amino-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine (50 mg, 0.121 mmol) was dissolved in chloroform (3 ml). Phenylisocyanate (0.12 ml, 0.131 mmol) was added and the mixture stirred overnight. The solvent was removed under reduced pressure and the product was purified by preparatory HPLC to give the desired product. RT: 2.78 min, MI: 534, Method: 2. 1H NMR (DMSO, 300 MHz): 1.76 (m, 4H), 2.80 (m, 4H), 2.99 (t, 2H), 3.99 (t, 2H), 6.86 (d, 2H), 6.94 (t, 1H), 7.13 (d, 1H), 7.26 (t, 2H), 7.34-7.66 (m, 9H), 8.32 (s, 1H), 9.43 (bs, 1H), 9.68 (bs, 1H), 9.81 (s, br, 1H).
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:5]([CH2:24][CH2:25][CH2:26][CH3:27])=[N:4][C:3]=1[CH3:28].[CH3:29][C:30]1[C:34](B(O)O)=[C:33]([CH3:38])[O:32][N:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:24]([C:5]1[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7](=[O:8])[C:2]([C:34]2[C:30]([CH3:29])=[N:31][O:32][C:33]=2[CH3:38])=[C:3]([CH3:28])[N:4]=1)[CH2:25][CH2:26][CH3:27]
Reactant: CCCCc1nc(C)c(Br)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: Cc1noc(C)c1B(O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CCCCc1nc(C)c(-c2c(C)noc2C)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 90 °C
Reaction time: 12 h
Yield: 30.9 %

Procedure:
To a solution of 4′-[(5-bromo-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl]biphenyl-2-carbonitrile (1 g) and 3,5-dimethylisoxazol-4-ylboronic acid (0.48 g) in 1,4-dioxane (20 mL) were added 2 M aqueous cesium carbonate solution (4 mL) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.1 g), and the mixture was stirred at 90° C. for 12 hr under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off through celite. The filtrate was washed successively with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (0.32 g, 31%) as a pale-yellow solid.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH3:9].C([Li:14])(C)(C)C.C=CC=C.C=CC1C=CC=CC=1>C1CCCCC1.CCCCC>[Li:14][CH2:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH3:9]
Reactant: CN1CCCC1CCCl
Reactant: [Li]C(C)(C)C
Agent: C=CC=C
Solvent: C=Cc1ccccc1
Solvent: CCCCC
Solvent: C1CCCCC1
Product: [Li]CCC1CCCN1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-(2-chloroethyl)-1-methylpyrrolidine was dissolved in cyclohexane and reacted with about two molar equivalents of t-butyllithium in pentane in an inert atmosphere including argon or nitrogen. The resulting mixture was agitated gently at room temperature for about an hour. The mixture was allowed to stand overnight and used to initiate the polymerization of butadiene and styrene as described in the following examples.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C@@H:20]([OH:23])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.O>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](O)C1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(=O)C1
Reaction time: 0.25 h
Yield: 97.6 %

Procedure:
A solution of 3.4 ml of dimethylsulfoxide in 10 ml of methylene chloride was added to a solution of 2.0 ml oxalyl chloride in 50 ml of methylene chloride, maintained at -50° to -60° C., and immediately afterwards a solution of 3.74 g of (3R)-1-(t-butoxycarbonyl)-3-hydroxypyrrolidine in 20 ml of methylene chloride was added to the mixture over a period of about 2 minutes. The reaction mixture was kept stirred for 15 minutes at -50° to -60° C., and then 14 ml of triethylamine were added to it. The mixture was stirred at the same temperature for a further 5 minutes, and the stirring was then continued while allowing its temperature to rise to ambient. The reaction mixture was mixed with 100 ml of water and extracted with methylene chloride. The organic extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was chromatographed on a silica gel column, eluted with a 2/1 mixture of benzene and ethyl acetate, giving 3.61 g of 1-(t-butoxycarbonyl)-3-pyrrolidone as an oil.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][CH2:11][CH2:12][OH:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[CH2:15][C:16]([OH:18])=[O:17]>CN(C)C(=O)C>[CH2:3]([O:10][CH2:11][CH2:12][O:13][CH2:15][C:16]([OH:18])=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCCOCc1ccccc1
Reactant: O=C(O)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: O=C(O)COCCOCc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 102.4 %

Procedure:
Sixty % sodium hydride in oil (6.80 g) is suspended in N,N-dimethylacetamide (80 ml) and a solution of 2-(benzyloxy)ethanol (12.9 g) in N,N-dimethylacetamide (50 ml) is added dropwise to the mixture over 10 minutes under ice-cooling. After stirring at room temperature for 15 minutes, the reaction solution is cooled with ice, and thereto is added chloroacetic acid (8.13 g) in small portions. The mixture is then stirred at room temperature for 11 hours. The reaction solution is concentrated under reduced pressure, and to the resulting residue is added aqueous sodium hydrogen carbonate solution and the mixture is washed with diethyl ether. The aqueous layer is acidified with conc. hydrochloric acid, and then extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over sodium sulfate and evaporated to remove solvent under reduced pressure to give [2-(benzyloxy)ethoxy]acetic acid (18.24 g).
Reaction SMILES: [C:1](=[O:6])([O:3][CH2:4][CH3:5])[NH2:2].[CH:7]12[CH2:13][CH:10]([CH2:11][CH2:12]1)[CH:9]=[CH:8]2>C(O)C>[C:7]12([NH:2][C:1](=[O:6])[O:3][CH2:4][CH3:5])[CH2:13][CH:10]([CH2:11][CH2:12]1)[CH2:9][CH2:8]2
Reactant: C1=CC2CCC1C2
Reactant: CCOC(N)=O
Solvent: CCO
Product: CCOC(=O)NC12CCC(CC1)C2
Temperature: 70 °C
Reaction time: 7 h
Yield: 85.8 %

Procedure:
A stirred mixture of 178 g of ethyl carbamate, 94 g of norbornene, 5 g of ethanol and 20 g of ®LEWASORB AC-10 was heated to 70° C. in a stirred reactor, and stirring was continued at this temperature for 7 hours. Thereafter, the catalyst was filtered off and the mixture was distilled under reduced pressure. 157 g (86% of theory) of ethyl N-norbornylcarbamate of boiling point 148°-150° C./20 mbar and melting point 50° C. (from pentane) were obtained. No substantial amount of norbornene oligomers was detected.
Reaction SMILES: [CH2:1]([N:3]1[N:7]=[N:6][C:5]([NH2:8])=[N:4]1)[CH3:2].N1C=CC=CC=1.[C:15]1([O:21][C:22](Cl)=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[C:15]1([O:21][C:22](=[O:23])[NH:8][C:5]2[N:6]=[N:7][N:3]([CH2:1][CH3:2])[N:4]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CCn1nnc(N)n1
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCn1nnc(NC(=O)Oc2ccccc2)n1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of 2-ethyl-2H-tetrazol-5-ylamine (0.1 g, 0.88 mmol) in dry THF (2 ml) is treated with pyridine (0.09 ml, 1.10 mmol) followed by a solution of phenylchloroformate (0.11 ml, 0.911 mmol) in THF (1 ml). The reaction mixture is stirred at ambient temperature for 1.5 hours, then partitioned between ethylacetate and water. The ethylacetate phase is dried over magnesium sulphate and evaporated to afford (2-Ethyl-2H-tetrazol-5-yl)-carbamic acid phenyl ester as a white solid. 1H NMR (CDCl3, 400 MHz) δ, 7.90 (1H, brs), 7.30 (2H, m), 7.15, (3H, m), 4.60 (2H, q) 1.60 (3H, t).