Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:8][C:5]([CH2:6][SH:7])=[CH:4][CH:3]=1.S(OC)(O[CH3:13])(=O)=O>>[CH3:13][S:7][CH2:6][C:5]1[O:8][C:2]([CH3:1])=[CH:3][CH:4]=1.[CH3:1][C:2]1[O:8][C:5]([CH2:6][SH:7])=[CH:4][CH:3]=1
Reactant: COS(=O)(=O)OC
Agent: Cc1ccc(CS)o1
Product: CSCc1ccc(C)o1

Procedure:
a. 5 -Methylfurfuryl methyl sulfide was prepared by reacting 5-methylfurfuryl-mercaptan with dimethyl sulfate in alkaline solution according to known methods. 5-Methylfurfuryl-mercaptan was obtained from the corresponding alcohol by the method described in Org.Syn. 35, 67 (1955). The product is a colorless liquid boiling at 71°-72° C./11 mm. Hg.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[CH2:3][N:4]=[C:5]([NH2:20])[NH:6][C:7]1[N:12]=[C:11]([S:13][CH2:14][CH2:15][CH2:16][C:17](O)=[O:18])[CH:10]=[CH:9][CH:8]=1.C([N:25](CC)CC)C.C(OC(Cl)=O)C(C)C.N>CN(C=O)C.CCO>[F:1][C:2]([F:22])([F:21])[CH2:3][N:4]=[C:5]([NH2:20])[NH:6][C:7]1[N:12]=[C:11]([S:13][CH2:14][CH2:15][CH2:16][C:17]([NH2:25])=[O:18])[CH:10]=[CH:9][CH:8]=1
Reactant: NC(=NCC(F)(F)F)Nc1cccc(SCCCC(=O)O)n1
Reactant: CCN(CC)CC
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: CN(C)C=O
Solvent: CCO
Product: NC(=O)CCCSc1cccc(NC(N)=NCC(F)(F)F)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 4-[6-(2-[2,2,2-trifluoroethyl]guanidino)pyrid-2-ylthio]butyric acid (84 mg.) and triethylamine (0.2 ml.) in DMF (5 ml.) was stirred at 0° while isobutylchloroformate (68 mg.) was added. The solution was kept at 0° for 0.5 hours, treated with a saturated solution of ammonia in EtOH (1 ml.) and then stirred at room temperature for 18 hours. The solution was evaporated to dryness and the residue partitioned between N aqueous HCl and EtOAc. The aqueous phase was basified with 10 N aqueous NaOH and extracted with EtOAc, and the extract was dried and evaporated to dryness to give 4-[6-(2-[2,2,2-trifluoroethyl]guanidino)pyrid-2-ylthio]butyramide (60 mg.) which was crystallised as the hydrogen maleate salt from acetone, m.p. 138°-141°.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=1.[CH2:11]([CH:13]1[O:15][CH2:14]1)Cl.C(O)C>O>[O:15]1[CH2:14][CH:13]1[CH2:11][NH:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=1
Reactant: ClCC1CO1
Reactant: N#CCc1ccc(N)cc1
Solvent: CCO
Solvent: O
Product: N#CCc1ccc(NCC2CO2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 50.8 %

Procedure:
A mixture of 4-aminobenzylcyanide (10 g, 75.7 mmol), epichlorohydrine (7.9 ml, 9.25 g, 100 mmol), ethanol (15 ml) and water (10 ml) was heated under reflux for 2 hours. After cooling the reaction mixture was poured into 100 ml of water and extracted with ether (3×50 ml). The organic extracts were combined and stirred with 50 ml of 10N NaOH at room temperature for 3 hours. The organic layer was separated, washed with water until neutral, dried over MgSO4 and concentrated. The residue was chromatographed over a silica gel column eluting with a 3:1 mixture of benzene and ethyl acetate to afford 7.24 g of the title compound as an oil, yield: 51.0%.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[C:11]([CH3:17])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][N:19]([CH2:27][CH2:28][NH:29][CH3:30])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]([N:29]([CH3:30])[CH2:28][CH2:27][N:19]([CH3:18])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:16])=[C:11]([CH3:17])[CH:10]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1cc(NC(=O)OC(C)(C)C)sc1C(=O)O
Reactant: CNCCN(C)C(=O)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: Cc1cc(NC(=O)OC(C)(C)C)sc1C(=O)N(C)CCN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 76 %

Procedure:
The compound (600 mg, 2.33 mmol) obtained in Example 89a and tert-butyl methyl[2-(methylamino)ethyl]carbamate (439 mg, 2.33 mmol) described in the literature (J. Med. Chem. 1990, 33, 97) were dissolved in methylene chloride (23 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (670 mg, 3.50 mmol) and 4-dimethylaminopyridine (14 mg, 0.117 mmol) were added, and the mixture was stirred at room temperature for 1.5 hours. The solvent was evaporated under reduced pressure, 1 N hydrochloric acid was added to the resulting residue, the mixture was extracted with ethyl acetate, and then the organic layer was washed with saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1, v/v) to give the title compound (757 mg; yield, 79%) as a light yellow solid.
Reaction SMILES: [H-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10].[Cl:11][CH2:12][CH2:13][CH2:14]Br.O>CN(C)C=O>[Cl:11][CH2:12][CH2:13][CH2:14][O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[NH2:3]
Reactant: ClCCCBr
Reactant: Nc1ccccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccccc1OCCCCl
Temperature: 25 °C
Reaction time: 1 h
Yield: 12.6 %

Procedure:
To a stirred suspension of sodium hydride (11.0 g, 230 mmol of a 50% oil dispersion) in dimethylformamide (250 ml), under nitrogen, was added, dropwise, 2-aminophenol (25.0 g, 230 mmol) dissolved in dimethylformamide (125 ml). After complete addition, the reaction was stirred at ambient temperature for 1 hour, and then it was cooled to 5° C. (ice bath). 3-Chloro-1-bromopropane (36.2 g, 230 mmol) in dimethylformamide (50 ml) was added, dropwise, so that the temperature did not go above 8° C. The reaction was stirred for 4 hours and then permitted to stand at ambient temperature for 16 hours. The reaction was poured into water and extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent concentrated to afford 25.4 g of a reddish, dark oil. About 12.0 g of the oil was chromatographed on HPLC columns. Concentration of the largest fractions gave 5.4 g of 2-(3-chloropropoxy) aniline as an oil.
Reaction SMILES: N1C=CC=CC=1.[CH3:7][N:8]1[C:12](=[O:13])[C@H:11]([OH:14])[CH2:10][C@H:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1>CN(C=O)C.C1(=O)OC(=O)CC1>[CH3:7][N:8]1[C:12](=[O:13])[CH:11]([OH:14])[CH2:10][CH:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1
Reactant: CN1C(=O)[C@H](O)C[C@H]1c1cccnc1
Agent: O=C1CCC(=O)O1
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: CN1C(=O)C(O)CC1c1cccnc1

Procedure:
Hydroxycotinine hemisuccinate was prepared as follows. In a glass tube, 19 mg of trans-3'-hydroxycotinine were dissolved in 1 ml of DMF. In this solution 21 mg of succinic anhydride were dissolved. After adding 20 μl of pyridine, the tube was covered (PARAFILM®) and incubated overnight at 37° C.
Reaction SMILES: [C:1]([C:4]1[CH:22]=[CH:21][C:7]([O:8][CH2:9][CH2:10][O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[C:5]=1[OH:26])(=[O:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.[N:51]1[CH:56]=[CH:55][CH:54]=[C:53]([CH2:57][CH2:58][CH2:59][CH2:60][NH2:61])[CH:52]=1>CN(C=O)C>[C:1]([C:4]1[CH:22]=[CH:21][C:7]([O:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([C:16]([NH:61][CH2:60][CH2:59][CH2:58][CH2:57][C:53]3[CH:52]=[N:51][CH:56]=[CH:55][CH:54]=3)=[O:18])=[CH:19][CH:20]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[C:5]=1[OH:26])(=[O:3])[CH3:2]
Reactant: NCCCCc1cccnc1
Reactant: CCCc1c(OCCOc2ccc(C(=O)O)cc2)ccc(C(C)=O)c1O
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCc1c(OCCOc2ccc(C(=O)NCCCCc3cccnc3)cc2)ccc(C(C)=O)c1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
To a cold (0° C.) solution of 1.22 g of 4-[2-(4-Acetyl-3-hydroxy-2-propylphenoxy)ethoxy]benzoic acid in 15 mL of anhydrous DMF was added to 0.8 mL of diphenylphosphoryl azide and 1.05 mL of anhydrous triethylamine. The resulting mixture was stirred at 0° C. for one hour and then 0.56 g of 3-pyridine butanamine was added. The mixture was stirred in ice bath for 1 hour and at room temperature for 6 hours. The solvent was removed in vacuo, the residue was dissolved in methylene chloride and washed with sodium bicarbonate solution. The extract was dried (over magnesium sulfate) and concentrated in vacuo to an oil which was purified by HPLC using 7% methanol-ethyl acetate to give an oil which was triturated with ethyl acetate-ether and filtered to yield 1.0 g, mp 93° , (60% yield) of 4-[2-(4-Acetyl-3-hydroxy-2-propylphenoxy)-ethoxy]-N-[4-(3-pyridinyl)butyl]benzamide, the title compound.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][OH:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>C(Cl)Cl>[CH3:32][S:33]([O:22][CH2:21][C@H:9]1[CH2:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][CH2:13][N:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)(=[O:35])=[O:34]
Reactant: OC[C@H]1CN(Cc2ccccc2)CCN1Cc1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)OC[C@H]1CN(Cc2ccccc2)CCN1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.02 h
Yield: 87.5 %

Procedure:
A mixture of (R)-(1,4-dibenzylpiperazin-2-yl)methanol (4.00 g, 13.49 mmol, US2007/0088039) and Hünig's base (2.35 mL, 13.49 mmol) in CH2Cl2 (27 mL) was stirred at 0° C. and methanesulfonyl chloride (1.04 mL, 13.49 mmol) was added drop-wise. The reaction mixture was filtered through a short pad of silica gel, using 19:1 CH2Cl2/Et2O (1000 mL) to rinse. The filtrate was concentrated in vacuo while maintaining the temperature below 25° C. Diethyl ether was added to the residue, the resulting slurry was placed in a sonicator for 1 min, filtered through a fitted funnel and the filtrate was concentrated to give a white solid ((2R)-1,4-dibenzyl-2-piperazinyl)methyl methanesulfonate (4.42 g).
Reaction SMILES: [F:1][C:2]1([F:22])[CH2:6][C@H:5]([CH:7]=O)[N:4]([CH2:9][CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)[C:3]1=[O:21].COP([CH2:29][C:30](=[O:38])[CH:31]([CH3:37])[CH2:32][C:33]#[C:34][CH2:35][CH3:36])(=O)OC>>[F:1][C:2]1([F:22])[CH2:6][C@H:5](/[CH:7]=[CH:29]/[CH:30]([OH:38])[CH:31]([CH3:37])[CH2:32][C:33]#[C:34][CH2:35][CH3:36])[N:4]([CH2:9][CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)[C:3]1=[O:21]
Reactant: CCC#CCC(C)C(=O)CP(=O)(OC)OC
Reactant: COC(=O)c1ccc(CCN2C(=O)C(F)(F)C[C@@H]2C=O)cc1
Product: CCC#CCC(C)C(O)/C=C/[C@H]1CC(F)(F)C(=O)N1CCc1ccc(C(=O)OC)cc1

Procedure:
Methyl 4-(2-((5R)-3,3-difluoro-5-((E)-3-hydroxy-4-methylnon-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)ethyl)benzoate was prepared by the method described in Example 1, Steps A and B, except that (R)-methyl 4-(2-(3,3-difluoro-5-formyl-2-oxopyrrolidin-1-yl)ethyl)benzoate (13b) was used instead of (R)-methyl 7-(3,3-difluoro-5-formyl-2-oxopyrrolidin-1-yl) heptanoate (13a) and (±)-dimethyl(3-methyl-2-oxooct-5-yn-1-yl)phosphonate (15bb(i)/15bc(i)) was used instead of (±)-dimethyl(3-methyl-2-oxohept-5-yn-1-yl)phosphonate (15ab(i)/15ac(i)) in Step A.
Reaction SMILES: [Br:1][C@H:2]1[CH2:21][C@@:20]2([CH3:22])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:19]2[C:18](=[O:23])[CH2:17][C@@:16]2([CH3:24])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[CH2:4][C@@H:3]1[OH:25].[C:26](OC(=O)C)(=[O:28])[CH3:27].O>N1C=CC=CC=1>[C:26]([O:25][C@@H:3]1[C@@H:2]([Br:1])[CH2:21][C@@:20]2([CH3:22])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:19]2[C:18](=[O:23])[CH2:17][C@@:16]2([CH3:24])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[CH2:4]1)(=[O:28])[CH3:27]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](Br)C[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]3[C@@]2(C)C[C@@H]1Br
Reaction time: 8 h

Procedure:
2β-Bromo-3α-hydroxy-5α-pregnane-11,20-dione (750 mg.) in pyridine (2 ml.) was treated with acetic anhydride (1 ml.) and the mixture was allowed to stand at room temperature overnight. It was then poured into water to give a white solid (720 mg.) which was recrystallised from methanol to give the title compound (471 mg.) as white crystals, m.p. 154°-156°, [α]D + 128.5°.
Reaction SMILES: [C:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH:23]2[CH2:25][CH2:24]2)[C:10](=[O:22])[C:11]2[CH:16]=[CH:15][C:14]([C:17]3[O:21][CH:20]=[N:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:5][CH2:4]1)#[N:2].[OH:26][NH:27][C:28](=N)[CH2:29][CH:30]=[CH2:31]>>[CH2:29]([C:28]1[N:2]=[C:1]([N:3]2[CH2:4][CH2:5][CH:6]([N:9]([CH:23]3[CH2:25][CH2:24]3)[C:10](=[O:22])[C:11]3[CH:12]=[CH:13][C:14]([C:17]4[O:21][CH:20]=[N:19][CH:18]=4)=[CH:15][CH:16]=3)[CH2:7][CH2:8]2)[O:26][N:27]=1)[CH:30]=[CH2:31]
Reactant: C=CCC(=N)NO
Reactant: N#CN1CCC(N(C(=O)c2ccc(-c3cnco3)cc2)C2CC2)CC1
Product: C=CCc1noc(N2CCC(N(C(=O)c3ccc(-c4cnco4)cc3)C3CC3)CC2)n1

Procedure:
The title compound is prepared from N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide and N-hydroxy-but-3-enamidine following a procedure analogous to that described in Example 1. LC (method 6): tR=1.65 min; Mass spectrum (ESI+): m/z=420 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[C:7]([CH3:13])[C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH2:16])=[O:15].[O:17]1[C:21]2=[CH:22][CH:23]=[CH:24][C:25]([NH2:26])=[C:20]2[CH2:19][CH2:18]1.Cl.IC1C=C2C(=CC=1)N=CC(C(N)=O)=C2NC1C=CC=C(OC)C=1>C(#N)C>[ClH:1].[Cl:12][C:8]1[C:7]([CH3:13])=[C:6]2[C:11]([C:2]([NH:26][C:25]3[C:20]4[CH2:19][CH2:18][O:17][C:21]=4[CH:22]=[CH:23][CH:24]=3)=[C:3]([C:14]([NH2:16])=[O:15])[CH:4]=[N:5]2)=[CH:10][CH:9]=1
Reactant: Nc1cccc2c1CCO2
Reactant: Cc1c(Cl)ccc2c(Cl)c(C(N)=O)cnc12
Agent: COc1cccc(Nc2c(C(N)=O)cnc3ccc(I)cc23)c1
Agent: Cl
Solvent: CC#N
Product: Cc1c(Cl)ccc2c(Nc3cccc4c3CCO4)c(C(N)=O)cnc12

Procedure:
Intermediate 104 was prepared from Intermediate 68 using 2,3-dihydro-1-benzofuran-4-amine in a similar manner to Intermediate 14, using acetonitrile as solvent.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])[CH2:4][CH2:3]1.[C:18](O)(=[O:22])[C@@H:19]([CH3:21])[OH:20].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[OH:20][C@H:19]([CH3:21])[C:18]([NH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])[CH2:4][CH2:3]1)=[O:22]
Reactant: C[C@@H](O)C(=O)O
Reactant: C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CC[C@H](N)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C[C@@H](O)C(=O)N[C@H]1CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Trans-tert-butyl (R)-1-(4-aminocyclohexyl)ethylcarbamate (125 mg, 0.52 mmol) was dissolved in DMF (3 mL). D-Lactic Acid (49.52 mg, 0.52 mmol), diisopropylethylamine (166.6 mg, 224.5 μL, 1.29 mmol) and TBTU (165.6 mg, 0.5158 mmol) were successively added. The reaction mixture was allowed to stir at ambient temperature for 3 hours. The crude mixture was partitioned between ethyl acetate and brine. The organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by column chromatography (ISCO Companion□, 12 g column, 0-10% MeOH/DCM) to afford the title compound (66.1 mg, 41% yield).
Reaction SMILES: [NH2:1][C@@H:2]([CH3:5])[CH2:3][OH:4].[C:6](=O)([O:12]C(C)(C)C)[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>C1COCC1>[OH:4][CH2:3][C@@H:2]([NH:1][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:5]
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Reactant: C[C@H](N)CO
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@@H](CO)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (S)-2-aminopropan-1-ol (1 eq) in THF (0.3 M) at room temperature was added di-tert-butyl carbonate (1 eq) and triethylamine (1 eq). The reaction was stirred at room temperature for 3 hours. The reaction mixture was concentrated en vaccuo; and the residue was diluted in ethyl acetate. The organic solution was washed with water (2×), 1:1 saturated aqueous NH4Cl, water and brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The material was carried onto the next step without further purification.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[CH2:12]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=1)[CH:13]=[CH2:14]>ClCCl>[O:6]1[CH2:14][CH:13]1[CH2:12][C:15]1[CH:16]=[CH:17][C:18]([C:19]#[N:20])=[CH:21][CH:22]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=CCc1ccc(C#N)cc1
Solvent: ClCCl
Product: N#Cc1ccc(CC2CO2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.6 %

Procedure:
Add a solution of 3-chloro-peroxybenzoic acid (5.44 g, 40.92 mmol), in 25 ml of dichloromethane to a solution of 4-allyl-benzonitrile (2.66 g, 18.60 mmol) in 50 ml of dichloromethane. stir at room temperature overnight. Quench with NaHCO3 (15 ml) saturated solution and wash the organic layer three times with NaHCO3 solution and dry over magnesium sulfate. Evaporate in vacuo, and purify by flash chromatography in Hexane-AcOEt (7:1, 1% Et3N) affording 1.44 g (49%) of the title compound. MS m/z 160 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.[C:21](Cl)(=O)[CH2:22][CH2:23][CH2:24][CH3:25].O.C(=O)(O)[O-].[Na+]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:21]([CH2:22][CH2:23][CH2:24][CH3:25])=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1
Reactant: CCCCC(=O)Cl
Reactant: NNC1=Nc2ccc(Br)cc2C(c2ccccc2)=NC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCc1nnc2n1-c1ccc(Br)cc1C(c1ccccc1)=NC2
Temperature: 125 °C
Reaction time: 2.5 h

Procedure:
To a solution of 2 g of 7-bromo-2-hydrazino-5-phenyl-3H-[1,4]benzodiazepine in 60 ml of tetrahydrofuran cooled in an ice bath under a nitrogen atmosphere is added 0.87 ml of valeryl chloride dropwise over 3 min. After stirring for 2.5 hrs, the reaction mixture is then poured into 100 ml of water and aqueous sodium bicarbonate. A solid precipitate is then collected on a filter, washed with water and dried. The resulting residue is then dissolved in 25 ml of acetic acid, heated under a nitrogen atmosphere in an oil bath to 125° C. for 35 min, allowed to cool, and concentrated under reduced pressure. Crystallization of the residue from a mixture of methanol and water yields 0.88 g of title product with melting point 87°-90° C. and 0.41 g of title product with melting point 88°-90° C. as a monohydrate.
Reaction SMILES: Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[N:5][CH:4]=1.[Cl:23][C:24]1[C:30]([OH:31])=[CH:29][C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.C(O)(C)C>CC(O)CCC>[Cl:23][C:24]1[C:30]([OH:31])=[CH:29][C:27]([NH:28][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[N:5][CH:4]=2)=[C:26]([F:32])[CH:25]=1
Reactant: COc1cc2c(Cl)cnnc2cc1OCc1ccncc1
Reactant: Nc1cc(O)c(Cl)cc1F
Agent: Cl
Solvent: CC(C)O
Solvent: CCCC(C)O
Product: COc1cc2c(Nc3cc(O)c(Cl)cc3F)cnnc2cc1OCc1ccncc1

Procedure:
A suspension of 4-chloro-6-methoxy-7-(4-pyridylmethoxy)cinnoline hydrochloride (0.17 g, 0.45 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (102 mg, 0.63 mmol), (prepared as described in EP 061741 A2), in 2-pentanol (3.5 ml) was heated at reflux overnight. After cooling, isopropanol was added. The solid formed was filtered off, washed with isopropanol, ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(4-pyridylmethoxy)cinnoline as the hydrochloride salt (yellow solid, 194 mg, 86%).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:23]=3[Cl:30])=[C:19]([CH2:31]Cl)[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:33]([CH2:35][NH2:36])[OH:34]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:23]=3[Cl:30])=[C:19]([CH2:31][NH:36][CH2:35][CH2:33][OH:34])[N:18]=[CH:17][N:16]=2)(=[O:12])=[O:13])=[CH:7][CH:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: NCCO
Reactant: COc1ccc(Cl)c(Oc2c(CCl)ncnc2NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1
Product: COc1ccc(Cl)c(Oc2c(CNCCO)ncnc2NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1

Procedure:
By reacting 4-tert-butyl-N-[6-chloromethyl-5-(2-chloro-5-methoxy-phenoxy)-pyrimidin-4-yl]-benzenesulphonamide with ethanolamine there was obtained 4-tert-butyl-N-[5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethylaminomethyl)-pyrimidin-4yl]-benzenesulphonamide.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH2:8]1[CH:12]2[CH:13]3[CH:17]=[CH:16][CH:15]([CH:11]2[CH:10]=[CH:9]1)[CH2:14]3.[OH2:18]>>[C:1]([OH:6])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:18])=[O:5].[CH2:8]1[CH:12]2[CH:13]3[CH:17]=[CH:16][CH:15]([CH:11]2[CH:10]=[CH:9]1)[CH2:14]3
Reactant: O=C1C=CC(=O)O1
Reactant: O
Solvent: C1=CC2C3C=CC(C3)C2C1
Product: O=C(O)/C=C\C(=O)O

Procedure:
196 parts maleic anhydride, 278 parts (95% pure) dicyclopentadiene and 36 parts demineralized water were placed into a four-necked flask, and addition reaction was performed under nitrogen stream at 130° C. for 3 hours to obtain an addition product of maleic acid to dicyclopentadiene. Next, 118 parts phthalic anhydride and 124 parts ethylene glycol were added and mixed. Then the mixture was dehydrated and condensed in a widely-used manner under nitrogen stream at 200° C. for 8 hours to obtain a dicyclopentenyl-group-containing unsaturated polyester having an acid value of 25 mgKOH/g and a dicyclopentenyl group ratio of 38 percent by weight. This dicyclopentenyl-group-containing unsaturated polyester was dissolved at 80° C. in a solution in which 0.1 parts hydroquinone is dissolved in 310 parts styrene monomer. A dicyclopentenyl-group-containing unsaturated polyester resin (I) of a viscosity of 3.0 stokes/25° C. was thus obtained.