Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])[C:27]([OH:29])=O)#[N:23].O[NH:38][C:39](=[NH:58])[C:40]1[CH:48]=[C:47]2[C:43]([C:44]([CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[CH:45][NH:46]2)=[CH:42][CH:41]=1>CN(C=O)C>[C:22]([C:24]1[CH:25]=[C:26]([C:27]2[O:29][N:38]=[C:39]([C:40]3[CH:48]=[C:47]4[C:43]([C:44]([CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[CH:45][NH:46]4)=[CH:42][CH:41]=3)[N:58]=2)[CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])#[N:23]
Reactant: CC(C)(C)OC(=O)CCc1c[nH]c2cc(C(=N)NO)ccc12
Reactant: CC(C)Oc1ccc(C(=O)O)cc1C#N
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc(-c2nc(-c3ccc4c(CCC(=O)OC(C)(C)C)c[nH]c4c3)no2)cc1C#N
Temperature: 80 °C
Reaction time: 0.75 h
Yield: 33.9 %

Procedure:
EDCI (151 mg) and HOBT (121 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848, 135 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 45 min. 1,1-dimethylethyl 3-{6-[(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D16) (199 mg) was added and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was heated to 80° C. and stirred at that temperature for 5 hours. DMF was evaporated. EtOAc (100 mL) was added and the organic solution was washed with saturated aqueous sodium bicarbonate solution (75 mL) and water (75 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was purified by Biotage (25→33% EtOAc in hexane) to afford 1,1-dimethylethyl 3-[6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate (D19) (105 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.38 (9H, s), 1.39 (6H, d), 2.60 (2H, t), 2.96 (2H, t), 4.98 (1H, m), 7.35 (1H, d), 7.55 (1H, d), 7.72 (2H, m), 8.12 (1H, d), 8.42 (1H, dd), 8.51 (1H, d), 11.21 (1H, s). MS (ES): C27H28N4O4 requires 472; found 473.0 (M+H+).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:12]=[C:11]([N:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[CH:10]=[CH:9][C:6]=1[CH:7]=O)(=[O:3])[CH3:2].C([O-])(=O)C.[NH4+].[N+:23]([CH3:26])([O-:25])=[O:24]>>[CH2:14]([N:13]([C:11]1[CH:10]=[CH:9][C:6]([CH:7]=[CH:26][N+:23]([O-:25])=[O:24])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:12]=1)[CH2:16][CH3:17])[CH3:15]
Reactant: C[N+](=O)[O-]
Reactant: CCN(CC)c1ccc(C=O)c(OC(C)=O)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: CCN(CC)c1ccc(C=C[N+](=O)[O-])c(OC(C)=O)c1
Temperature: 100 °C
Yield: 36 %

Procedure:
A solution was prepared by dissolving 23.5 grams (0.10 mol) of 2-acetyloxy-4-(N,N-diethylamino)benzaldehyde in 100 ml of nitromethane, and added with 3 grams of ammonium acetate. The mixture was heated at 100° C. for 5 hours under agitation. The reaction solution was then cooled on a dry ice-acetone bath until crystallization had been completed. The separated solid (crystal) was filtered off and dried in vacuum. The obtained product was recrystallized from acetonitrile for two times. An amount of 10 grams of red crystals was obtained. The yield was 36%.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2.[CH:13]12[CH2:18][CH:17]1[C:16](=[O:19])[O:15][C:14]2=O>C(O)(=O)C>[O:12]=[C:7]1[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([CH2:2][N:1]3[C:14](=[O:15])[C@@H:13]4[C@@H:17]([CH2:18]4)[C:16]3=[O:19])[CH:4]=2)[NH:8]1
Reactant: O=C1OC(=O)C2CC12
Reactant: NCc1ccc2c(c1)CC(=O)N2
Solvent: CC(=O)O
Product: O=C1Cc2cc(CN3C(=O)[C@H]4C[C@H]4C3=O)ccc2N1

Procedure:
A solution of the compound obtained in Step C (15 mmoles) and 3-oxa-bicyclo[3.1.0]-hexane-2,4-dione (22.5 mmoles) in acetic acid (60 ml) is heated at reflux for 48 hours. The mixture is brought to ambient temperature and the solid formed is filtered off to yield the title product, which is used directly in the next reaction.
Reaction SMILES: [Br:1][CH:2]([Br:15])[C:3]1[N:8]=[C:7]([CH:9](Br)Br)[N:6]=[C:5]([CH:12]([Br:14])[Br:13])[N:4]=1.[I-].[Na+].S(=O)(O)[O-].[Na+]>CC(C)=O.C(O)(=O)C>[Br:14][CH:12]([Br:13])[C:5]1[N:4]=[C:3]([CH:2]([Br:1])[Br:15])[N:8]=[C:7]([CH3:9])[N:6]=1
Reactant: BrC(Br)c1nc(C(Br)Br)nc(C(Br)Br)n1
Agent: O=S([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: Cc1nc(C(Br)Br)nc(C(Br)Br)n1
Temperature: 0 °C

Procedure:
A solution of 2,4,6-tris(dibromomethyl)-s-triazine (15 g, 23.3 mmol) in acetone (100 mL) was added to a solution of sodium iodide (150 g, 1.0 mol) in acetic acid (50 mL) and acetone (500 mL). After 10 minutes at room temperature the reaction mixture was added to sodium bisulfite (25 g) in ice water (1000 mL). The aqueous layer was extracted with ether (3×100 mL). The ether layer was dried (MgSo4), filtered, and concentrated to dryness. The crude product was crystallized first from EtOH and then from cyclohexane to give the title compound (mp 87-88.5° C.). 1H NMR (CDCL3) δ2.51 (s, 3H, CH3), 6.86 (s, 2H, CH).
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([NH:9][C:10]([NH:12][C:13]2[N:14]=[C:15]3[CH:21]=[CH:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:16]3=[N:17][CH:18]=2)=[O:11])[CH2:4]1.[CH2:30]([S:33](Cl)(=[O:35])=[O:34])[CH2:31][CH3:32]>>[CH2:30]([S:33]([N:3]1[CH2:8][CH2:7][CH2:6][C@@H:5]([NH:9][C:10]([NH:12][C:13]2[N:14]=[C:15]3[CH:21]=[CH:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:16]3=[N:17][CH:18]=2)=[O:11])[CH2:4]1)(=[O:35])=[O:34])[CH2:31][CH3:32]
Reactant: C[Si](C)(C)CCOCn1ccc2nc(NC(=O)NC3CCCNC3)cnc21
Reactant: CCCS(=O)(=O)Cl
Agent: Cl
Product: CCCS(=O)(=O)N1CCC[C@@H](NC(=O)Nc2cnc3c(ccn3COCC[Si](C)(C)C)n2)C1

Procedure:
1-[(R)-1-(Propane-1-sulfonyl)-piperidin-3-yl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea was prepared in the same manner from 1-piperidin-3-yl-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea dihydrochloride and n-propylsulfonyl chloride.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7]Br)([O-:3])=[O:2].[P:12]([O:19]CC)([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15]>C1(C)C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][P:12](=[O:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])([O-:3])=[O:2]
Reactant: CCOP(OCC)OCC
Reactant: O=[N+]([O-])c1cccc(CBr)c1
Solvent: Cc1ccccc1
Product: CCOP(=O)(Cc1cccc([N+](=O)[O-])c1)OCC
Yield: 67.7 %

Procedure:
A mixture of 3-nitrobenzyl bromide (17.3 g, 0.08 mol), triethyl phosphite (13.3 g, 0.08 mol) in toluene (200 mL) was stirred at reflux for 24 h. The reaction mixture was cooled and evaporated in vacuo. Chromatography of the residues on SiO2 eluting from 0–100% ethyl acetate in petroleum ether (60–80° C.) gave the title compound (14.8 g, 68%) as a yellow liquid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7].[CH3:29][O:30][CH2:31][CH2:32][NH2:33]>>[CH3:29][O:30][CH2:31][CH2:32][NH:33][CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7]
Reactant: COc1ccc(C2CCOCC2)c2sc(NC(=O)c3ccnc(CCl)c3)nc12
Reactant: COCCN
Product: COCCNCc1cc(C(=O)Nc2nc3c(OC)ccc(C4CCOCC4)c3s2)ccn1

Procedure:
The title compound was prepared from 2-chloromethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-isonicotinamide and 2-methoxy-ethylamine in the same manner as described for N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-2-morpholin-4-ylmethyl-isonicotinarmide and afforded as yellow solid (60% yield). MS: m/e=457(M+H+), mp 93-95° C.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](Br)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[C:27](B(O)O)=[C:28]2[CH2:33][CH2:32][CH2:31][N:29]2[N:30]=1>C(Cl)Cl>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:27]3[C:26]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=4)=[N:30][N:29]4[CH2:31][CH2:32][CH2:33][C:28]=34)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(c1ccccc1)n1cc(Br)c2ccccc21
Reactant: OB(O)c1c(-c2ccccn2)nn2c1CCC2
Solvent: ClCCl
Product: O=S(=O)(c1ccccc1)n1cc(-c2c(-c3ccccn3)nn3c2CCC3)c2ccccc21

Procedure:
The titled intermediate was made via Preparation 33 (General Suzuki Coupling Method D) from 1-benzene-sulfonyl-3-bromo-1H-indole (Maybridge) and 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5). MS (ESI) m/e 441 (M+1). TLC (SiO2): Rf0.5 (1:1 methylene chloride/[80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]).
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[CH:27]([O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)([CH3:29])[CH3:28]>>[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([O:30][CH:27]([CH3:29])[CH3:28])[CH:36]=2)=[CH:13][CH:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)Oc1cccc(B(O)O)c1
Reactant: CC(C)(C)OC(=O)NC(C(=O)c1ccc(I)cc1)c1ccc(Cl)c(Cl)c1
Product: CC(C)Oc1cccc(-c2ccc(C(=O)C(NC(=O)OC(C)(C)C)c3ccc(Cl)c(Cl)c3)cc2)c1

Procedure:
The title compound was prepared from rac-[1-(3,4-dichloro-phenyl)-2-(4-iodo-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester and 3-isopropoxyphenylboronic acid in analogy to Example 2b): MS (ISN): 512.3 and 514.3 (M−H)−.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[C:8]([SH:10])[N:7]2[N:11]=[C:12]([CH2:14][OH:15])[N:13]=[C:6]2[N:5]=1)([OH:3])=[O:2].CC(O[CH2:20][C:21]1[CH2:30][S:29][C@@H:24]2[C@H:25]([NH2:28])[C:26](=[O:27])[N:23]2[C:22]=1[C:31]([OH:33])=[O:32])=O.O.N>C(#N)C>[NH2:28][CH:25]1[C:26](=[O:27])[N:23]2[C:22]([C:31]([OH:33])=[O:32])=[C:21]([CH2:20][S:10][C:8]3[N:7]4[N:11]=[C:12]([CH2:14][OH:15])[N:13]=[C:6]4[N:5]=[C:4]([C:1]([OH:3])=[O:2])[CH:9]=3)[CH2:30][S:29][C@H:24]12
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: O=C(O)c1cc(S)n2nc(CO)nc2n1
Agent: N
Solvent: O
Solvent: CC#N
Product: NC1C(=O)N2C(C(=O)O)=C(CSc3cc(C(=O)O)nc4nc(CO)nn34)CS[C@H]12
Temperature: 25 °C
Reaction time: 5 h
Yield: 65.8 %

Procedure:
In 130 ml of acetonitrile were suspended 8 g of 5-carboxy-2-hydroxymethyl-7-mercapto-s-triazolo[1,5-a]pyrimidine and 9.53 g of 7-aminocephalosporanic acid and 17 ml of boron trifluoride - ethyl ether complex was added thereto, and the mixture was stirred at room temperature for 5 hours. To the reaction mixture was added 300 ml of water and the mixture was adjusted to pH 2 with conc. aqueous ammonia. Precipitated crystals were collected by filtration, washed with water and with acetone, and dried to obtain 10.1 g of the title compound.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1>[Rh]>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[NH:5][CH:4]([CH3:13])[CH2:3][CH2:2]2
Reactant: Cc1cc(Cl)c2cc(F)ccc2n1
Agent: [Rh]
Product: CC1CCc2cc(F)ccc2N1

Procedure:
4-Chloro-6-fluoroquinaldine was reduced with rhodium on carbon to give 6-fluoro-2-methyltetrahydroquinoline.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[N:8]=[C:7]2[C:17]1[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=1.B(Br)(Br)Br.C1CCCCC=1>>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[N:8]=[C:7]2[C:17]1[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=1
Reactant: COc1ccc(-c2nn(C3CCCCC3)c3c(Cl)cccc23)cc1
Agent: BrB(Br)Br
Solvent: C1=CCCCC1
Product: Oc1ccc(-c2nn(C3CCCCC3)c3c(Cl)cccc23)cc1
Yield: 49.4 %

Procedure:
Prepared according to Method C step B from 7-chloro-1-cyclohexyl-3-(4-methoxyphenyl)-1H-indazole (0.55 g, 1.61 mmol), boron tribromide (0.61 mL, 6.5 mmol) and 1.0 mL of cyclohexene to give the product (0.26 g) as an off-white solid.
Reaction SMILES: [C:1]([C:9]1[C:10](=[O:20])[N:11]([CH3:19])[C:12](=[O:18])[N:13]([CH3:17])[C:14]=1[CH2:15]Br)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:21][C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1[OH:31]>CO>[OH:31][C:23]1[CH:24]=[CH:25][C:26]([N+:28]([O-:30])=[O:29])=[CH:27][C:22]=1[N:21]1[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:9]2[C:14]([N:13]([CH3:17])[C:12](=[O:18])[N:11]([CH3:19])[C:10]2=[O:20])=[CH:15]1
Reactant: Cn1c(CBr)c(C(=O)c2ccccc2)c(=O)n(C)c1=O
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Solvent: CO
Product: Cn1c(=O)c2c(-c3ccccc3)n(-c3cc([N+](=O)[O-])ccc3O)cc2n(C)c1=O
Yield: 113.3 %

Procedure:
In a 25 mL round bottom flask was placed 4a (1.00 g, 2.97 mmol) (see Example 2 for synthesis of 4a), 2-amino-4-nitrophenol (921 mg, 5.98 mmol), and methanol (12 mL). The reaction was stirred at reflux for 5 h, then cooled in an ice bath. The precipitate was filtered and rinsed with cold methanol to give 5g (1.32 g, 94%). 1H NMR (600 MHz, DMSO-d6) δ 11.72 (s, 1H), 8.19 (d, J=2.8, 1H), 8.15 (dd, J=2.9, 9.1, 1H), 7.31-7.21 (m, 5H), 7.08 (s, 1H), 7.01 (d, J=9.1, 1H), 3.34 (s, 3H), 3.21 (s, 3H). 13C NMR (151 MHz, DMSO-d6) δ 159.26, 159.03, 150.85, 138.89, 134.18, 130.34, 129.34, 128.85, 128.14, 127.36, 126.15, 126.09, 125.45, 116.60, 105.95, 102.41, 31.52, 27.48. MS (ES+) (m/z): [M+1]+ calculated for C20H17N4O5, 393.12. found 393.02.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:35])=[C:21]([NH:25][S:26]([N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[NH4+:36].[OH-]>>[NH2:36][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:35])=[C:21]([NH:25][S:26]([N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1
Reactant: O=S(=O)(Nc1cccc(-c2nc(N3CCOCC3)sc2-c2ccnc(Cl)n2)c1F)N1CCCCC1
Reactant: [NH4+]
Agent: [OH-]
Product: Nc1nccc(-c2sc(N3CCOCC3)nc2-c2cccc(NS(=O)(=O)N3CCCCC3)c2F)n1

Procedure:
Following a procedure analogous to the procedure described in Example 21 using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-1-piperidinesulfonamide (190 mg, 0.352 mmol) and NH4OH (4 mL) in a microwave reactor for 75 min at 120° C., the title compound was obtained an off-white solid (75 mg, 41% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.69 (s, 1H) 7.83 (d, J=5.3 Hz, 1H) 7.51 (td, J=7.4, 2.2 Hz, 1H) 7.05-7.38 (m, 2H) 6.54 (s, 2H) 5.79 (d, J=5.3 Hz, 1H) 3.68 (t, J=4.7 Hz, 4H) 3.43 (t, J=4.6 Hz, 4H), 3.01 (t, J=5.0 Hz, 4H) 1.33-1.52 (m, 6H). MS (ESI): 520.0 [M+H]+.
Reaction SMILES: [CH3:1][N:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([N:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=2)=[CH2:11])=[CH:6][CH:5]=1)[CH3:3].[CH3:21][N:22]([CH3:40])[C:23]1[CH:39]=[CH:38][C:26]([CH:27](O)[C:28]2[CH:33]=[CH:32][C:31]([N:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=2)=[CH:25][CH:24]=1.S(C1C=CC(C)=CC=1)(O)(=O)=O>CO>[CH3:20][N:18]([C:15]1[CH:14]=[CH:13][C:12]([C:10]([C:7]2[CH:8]=[CH:9][C:4]([N:2]([CH3:1])[CH3:3])=[CH:5][CH:6]=2)=[CH:11][CH:27]([C:26]2[CH:25]=[CH:24][C:23]([N:22]([CH3:21])[CH3:40])=[CH:39][CH:38]=2)[C:28]2[CH:29]=[CH:30][C:31]([N:34]([CH3:35])[CH3:36])=[CH:32][CH:33]=2)=[CH:17][CH:16]=1)[CH3:19]
Reactant: CN(C)c1ccc(C(O)c2ccc(N(C)C)cc2)cc1
Reactant: C=C(c1ccc(N(C)C)cc1)c1ccc(N(C)C)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: CN(C)c1ccc(C(=CC(c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)cc1

Procedure:
Michler's Ethylene (5g) and of 4,4'-bis-(dimethylamino)-benzhydrol (5g, Michler's Hydrol) were dissolved in methanol (50g) and 4-sulphotoluene (0.1g) was added. After stirring and heating under reflux for 2 hours, the insoluble crude product was isolated by filtration, washed with methanol and crystallised from toluene as a white solid (7g), MP 189°-190° C. It has the structure: ##STR12## Use of TDPP as a colour former in a pressure-sensitive copying paper
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=O.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[N:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1>ClCCl.O.N1C=CC=CC=1>[N:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:6]([C:2]3[NH:1][CH:5]=[CH:4][CH:3]=3)=[O:8])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1
Reactant: Nc1ccc(-c2ccncc2)cc1
Reactant: O=C(O)c1ccc[nH]1
Agent: O=C(Cl)C(=O)Cl
Solvent: c1ccncc1
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Nc1ccc(-c2ccncc2)cc1)c1ccc[nH]1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 61.2 %

Procedure:
To a mixture of 1H-pyrrole-2-carboxylic acid (45.0 mg) in dichloromethane (1.8 mL) were added oxalyl chloride (0.053 mL) and one-drop of N,N-dimethylformamide at 0° C. After 15 minutes, [4-(4-pyridinyl)phenyl]amine (68.9 mg) and pyridine (0.131 mL) were added to the mixture at 0° C. and the resulting mixture was stirred at ambient temperature overnight. Water (3 mL) was added to the mixture. The precipitate was collected by filtration and washed with water (2 mL) to afford N-[4-(4-pyridinyl)phenyl]-1H-pyrrole-2-carboxamide (65.2 mg) as white crystals.
Reaction SMILES: Cl.[OH:2][C:3]1[C:4]2[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=2[O:6][C:7]=1[C:8](=[NH:12])[O:9]CC.CC(=NN)C>C1C=CC=CC=1>[OH:2][C:3]1[C:4]2[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=2[O:6][C:7]=1[C:8](=[NH:12])[OH:9]
Reactant: CCOC(=N)c1oc2ccccc2c1O
Agent: CC(C)=NN
Agent: Cl
Solvent: c1ccccc1
Product: N=C(O)c1oc2ccccc2c1O
Yield: 95.4 %

Procedure:
A suspension of ethyl 3-hydroxybenzo[b]furan-2-carboximidate hydrochloride (8.86 g 36.7 mmol, described in Example 4) in benzene (400 mL) was combined with freshly prepared acetone hydrazone (8.0 g, 110 mmol). A solution was formed then a precipitate occurred. The mixture was refluxed for 1.5 hr, additional acetone hydrazone (5.0 g, 69 mmol) was added and the solution was refluxed for 0.5 hr. The reaction mixture was filtered hot to remove the precipitate (discarded), the filtrate was evaporated to dryness and the residue was triturated with diethyl ether to give 6.2 g of 3-hydroxybenzo[b]furan-2-carboximidic acid, 2-(2-propanehydrazide), the mp of which, 218°-220° C. (dec.), remained constant on recrystallization from acetonitrile: IR (mineral oil) 3411, 3120, 1640, 1600, 1520, 1450, 1100 and 1190 cm-1 ; NMR (DMSO-d6) δ1.95 (3H, s), 2.00 (3H, s), 7.3 and 7.6 (4 H, m), and ca. 7.6 (2H).
Reaction SMILES: [F:1][C:2]1[CH:32]=[CH:31][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]3[OH:30])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.Cl[CH2:34][C:35]1[CH:36]=[CH:37][C:38]2[O:43][CH2:42][C:41](=[O:44])[N:40]([CH2:45][CH2:46][CH2:47][O:48][CH3:49])[C:39]=2[CH:50]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:19][CH:18]3[O:30][CH2:34][C:35]3[CH:36]=[CH:37][C:38]4[O:43][CH2:42][C:41](=[O:44])[N:40]([CH2:45][CH2:46][CH2:47][O:48][CH3:49])[C:39]=4[CH:50]=3)=[CH:15][CH:16]=2)=[CH:31][CH:32]=1
Reactant: COCCCN1C(=O)COc2ccc(CCl)cc21
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCCOc3ccc(F)cc3)cc2)C(O)C1
Product: COCCCN1C(=O)COc2ccc(COC3CN(C(=O)OC(C)(C)C)CCC3c3ccc(OCCCOc4ccc(F)cc4)cc3)cc21

Procedure:
Analogously to Method D, 0.600 g of tert-butyl 4-{4-[3-(4-fluorophenoxy)propoxy]phenyl}-3-hydroxypiperidine-1-carboxylate and 0.408 g of 6-chloromethyl-4-(3-methoxypropyl)-4H-benzo[1,4]oxazin-3-one (Example 2a) are reacted. The title compound is obtained as a yellowish oil. Rf=0.17 (1:2 EtOAc-heptane); Rt=5.82.
Reaction SMILES: C1(COC(=O)[N:10]([C@H:19]([C:21]2[N:30](COCC[Si](C)(C)C)[C:24]3=[N:25][CH:26]=[C:27](Br)[CH:28]=[C:23]3[N:22]=2)[CH3:20])COCC[Si](C)(C)C)C=CC=CC=1.[CH2:40]([C@@H:42]1[CH2:51][C:50]2[N:49]=[CH:48][N:47]=[C:46]([N:52]3[CH2:58][C:57]4[CH:59]=[C:60](B(O)O)[CH:61]=[CH:62][C:56]=4[O:55][CH2:54][CH2:53]3)[C:45]=2[CH2:44][CH2:43]1)[CH3:41]>>[CH2:40]([C@@H:42]1[CH2:51][C:50]2[N:49]=[CH:48][N:47]=[C:46]([N:52]3[CH2:58][C:57]4[CH:59]=[C:60]([C:27]5[CH:28]=[C:23]6[NH:22][C:21]([C@@H:19]([NH2:10])[CH3:20])=[N:30][C:24]6=[N:25][CH:26]=5)[CH:61]=[CH:62][C:56]=4[O:55][CH2:54][CH2:53]3)[C:45]=2[CH2:44][CH2:43]1)[CH3:41]
Reactant: CC[C@H]1CCc2c(ncnc2N2CCOc3ccc(B(O)O)cc3C2)C1
Reactant: C[C@@H](c1nc2cc(Br)cnc2n1COCC[Si](C)(C)C)N(COCC[Si](C)(C)C)C(=O)OCc1ccccc1
Product: CC[C@H]1CCc2c(ncnc2N2CCOc3ccc(-c4cnc5nc([C@H](C)N)[nH]c5c4)cc3C2)C1

Procedure:
Prepared according to the method of example 5 by using phenylmethyl{(1S)-1-[6-bromo-3-({[2-(trimethylsilyl)ethyl]oxy}methyl)-3H-imidazo[4,5-b]pyridin-2-yl]ethyl}({[2-(trimethylsilyl)ethyl]oxy}methyl)carbamate (reagent preparation 19) and {4-[(7S)-7-ethyl-5,6,7,8-tetrahydroquinazolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}boronic acid (reagent preparation 23) in step 1. 1H NMR (400 MHz, Methanol-d4): 8.56 (s, 1H), 8.31 (s, 1H), 8.15 (s, 1H), 7.59 (s, 1H), 7.50 (d, 1H), 7.07 (d, 1H), 4.80 (m, 2H), 4.60 (q, 1H), 4.44 (m, 1H), 4.26 (m, 1H), 4.07 to 3.91 (m, 2H), 2.96 to 2.81 (m, 2H), 2.60 (m, 1H), 2.33 (m, 1H), 1.98 (m, 1H), 1.73 (m, 1H), 1.68 (d, 3H), 1.41 (m, 2H), 1.16 (m, 1H), 0.99 (t, 3H); MS (EI) for C27H31N7O: 470 (MH+).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH:16]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[N:19]=1)[OH:17])[CH2:13][CH2:14][CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([C:16]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[N:19]=1)=[O:17])[CH2:13][CH2:14][CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCC1(C(O)c2ccc(Cl)c(Cl)n2)CCCN1C(=O)OC(C)(C)C
Solvent: ClCCl
Product: CCCC1(C(=O)c2ccc(Cl)c(Cl)n2)CCCN1C(=O)OC(C)(C)C
Reaction time: 1 h
Yield: 97.7 %

Procedure:
To a stirred solution of 2-[(5,6-dichloro-pyridin-2-yl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.288 g, 0.742 mmol) in DCM (12 mL) at 0° C. under nitrogen was added DMP (0.315 g, 0.742 mmol) in a single portion. The reaction mixture was stirred for one hour, then was quenched with a 1:1 mixture of 10% aqueous Na2S2O3 and saturated aqueous NaHCO3 (50 mL), and extracted with DCM (3×30 mL). The combined organic phases were concentrated in vacuo to give 2-(5,6-dichloro-pyridine-2-carbonyl)-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.280 g, 0.725 mmol, 98%) as a yellow solid that was used directly without further purification.
Reaction SMILES: [OH-].[K+].CO.[OH:5][CH:6]([CH:12]([CH:16]([CH3:18])[CH3:17])[CH2:13][CH:14]=[CH2:15])[CH2:7][C:8]([O:10]C)=[O:9]>CO>[OH:5][CH:6]([CH:12]([CH:16]([CH3:18])[CH3:17])[CH2:13][CH:14]=[CH2:15])[CH2:7][C:8]([OH:10])=[O:9]
Reactant: C=CCC(C(C)C)C(O)CC(=O)OC
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: C=CCC(C(C)C)C(O)CC(=O)O
Temperature: 25 °C
Reaction time: 13 h

Procedure:
A 2 N potassium hydroxide-methanol solution (200 mL) was added to a methanol (132 mL) solution of methyl 3-hydroxy-4-isopropylhept-6-enoate (12.30 g, 61.5 mmol), and the mixture was stirred at room temperature for 13 hours. The solvent was distilled off under reduced pressure. To the residue, water and diethyl ether were then added, and the aqueous layer was neutralized with 2 N hydrochloric acid. Diethyl ether was added thereto, and the organic layer was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain the compound of interest as a brown oil substance (11.10 g, 97%).