Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]O)=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12].S(Cl)([Cl:16])=O>>[CH3:1][NH:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][Cl:16])=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12]
Reactant: O=S(Cl)Cl
Reactant: CNc1ccc(CO)cc1[N+](=O)[O-]
Product: CNc1ccc(CCl)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
1.0 g (5.5 mmol) of 9 was dissolved in 25 ml thionylchloride at -78° C. cooled with dry ice/acetone bath. After it dissolved completely, the dry ice/acetone bath was removed and the reaction mixture allowed to warm up to room temperature and kept at room temperature for additional 1 hour. Thionylchloride was evaporated under vacuum at room temperature and the residue was washed with 5 ml cold diethylether and recrystallized from diethylether to yield 0.6 g (55%) of 10. Yellow, mp: 126°-128° C. 1H NMR: (DMSO-d6): δ 82.9 (s, 1H, NH), 8.15 (d, 1H, J=2.2 Hz, H-2), 7.60p, 1H, (dd, 1H, J=8.9, 2.2 Hz, H-6), 7.01 (d, 1H, J=9.0 Hz, H-5), 4.76 (s, 3H, CH2), 2.95 (s, 3H, CH3). Anal. Calcd for C8H9N2O2Cl: C, 47.89; H, 4.52; Cl, 17.67; N, 14.00; O, 15.95. found: C, 47.78; H, 4.49; Cl, 17.78; N, 13.82; O, 16.13.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[C:15]3[S:16][CH:17]=[CH:18][C:14]=3[O:13][N:12]=2)[CH:8]=[CH:9][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:25][CH2:26][CH2:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>C(#N)C>[CH2:27]([CH:28]1[CH2:33][CH2:32][N:31]([CH2:2][CH2:3][O:4][C:5]2[CH:6]=[C:7]([C:11]3[C:15]4[S:16][CH:17]=[CH:18][C:14]=4[O:13][N:12]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:30][CH2:29]1)[CH2:26][CH3:25]
Reactant: CCCC1CCNCC1
Reactant: BrCCOc1cccc(-c2noc3ccsc23)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCC1CCN(CCOc2cccc(-c3noc4ccsc34)c2)CC1

Procedure:
The title compound is prepared from 3-[3-(2-bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole, potassium carbonate, 4-N-propylpiperidine and acetonitrile essentially as described above in example 40. Purity by LC/MS (APCI)=96%, [M+H]+=371.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]([NH2:15])[CH:3]1[OH:16])=[N:10][O:11][N:12]=3.C(N(CC)CC)C.[C:25](Cl)(=[O:28])[CH2:26][CH3:27]>C(Cl)Cl>[CH3:1][C:2]1([CH3:17])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]([NH:15][C:25](=[O:28])[CH2:26][CH3:27])[CH:3]1[OH:16])=[N:10][O:11][N:12]=3
Reactant: CC1(C)Oc2cc3nonc3cc2C(N)C1O
Reactant: CCC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCC(=O)NC1c2cc3nonc3cc2OC(C)(C)C1O
Temperature: 25 °C
Yield: 31 %

Procedure:
To a mixture of 200 mg (0.85 m mol) of 7,8-dihydro-6,6-dimethyl-7-hydroxy-8-amino-6H-pyrano [2,3-f] benzo-2,1,3-oxadiazole, 130 ml (0.935 m mol) of triethylamine and 20 ml of methylene chloride were added 81 μl (0.935 m mol) of propionyl chloride with stirring at the room temperature, followed by further stirring for 6 hours. After the completion of the reaction, the mixture solution was washed thrice with water and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to obtain 77 mg (yield: 31%) of the pure intended compound.
Reaction SMILES: [O:1]1[CH2:7][CH:2]1[CH2:3][CH2:4][CH:5]=[CH2:6].[CH3:8][O:9][SiH:10]([O:13][CH3:14])[O:11][CH3:12]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh].C1(C)C=CC=CC=1>[O:1]1[CH2:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][Si:10]([O:13][CH3:14])([O:11][CH3:12])[O:9][CH3:8]
Reactant: C=CCCC1CO1
Reactant: CO[SiH](OC)OC
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CO[Si](CCCCC1CO1)(OC)OC
Temperature: 80 °C
Yield: 61 %

Procedure:
In a 100 mL round-bottom flask were placed 8.5 mL of 5,6-epoxy-1-hexene (0.1 moles), 1.5 equivalents of trimethoxysilane (17 mL), 30 mL of toluene dried by refluxing with sodium benzophenone ketyl, and 3 mg of tris(triphenylphosphine)rhodium (I) chloride. The resulting light purple solution was stirred and heated at 80° C. for 12 hours. The solvent was removed under reduced pressure, and the resulting oil subjected to fractional vacuum distillation. 5,6-Epoxyhexyltrimethoxysilane was obtained (13.5 g, 61% yield) as a colorless liquid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9](CCCCCCCCCCCCCCC)[C:5]=1[C:6](Cl)=[O:7])[CH3:2].[NH2:28][C:29]1[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[C:31]([C:37]([F:40])([F:39])[F:38])[CH:30]=1.C(N(CC)CC)C>ClCCl>[C:33]([C:32]1[CH:35]=[CH:36][C:29]([NH:28][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=2[O:3][CH2:1][CH3:2])=[CH:30][C:31]=1[C:37]([F:38])([F:39])[F:40])#[N:34]
Reactant: CCCCCCCCCCCCCCCc1cccc(OCC)c1C(=O)Cl
Reactant: N#Cc1ccc(N)cc1C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOc1ccccc1C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1

Procedure:
2-ethoxy-6-pentadecyl-benzoyl chloride was condensed with 4-Amino-2-trifluoromethyl benzonitrile in dichloromethane in presence of triethylamine as acid scavenger to yield N-(4-Cyano-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[NH:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:3]1.[C:16]1([CH3:28])[CH:21]=[CH:20][C:19]([S:22]([N:25]=[C:26]=[O:27])(=[O:24])=[O:23])=[CH:18][CH:17]=1>C1C=CC=CC=1>[CH3:1][C:2]1([CH3:15])[N:6]([C:26](=[O:27])[NH:25][S:22]([C:19]2[CH:20]=[CH:21][C:16]([CH3:28])=[CH:17][CH:18]=2)(=[O:23])=[O:24])[CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:3]1
Reactant: Cc1ccc(S(=O)(=O)N=C=O)cc1
Reactant: CC1(C)NCC(COc2ccccc2)O1
Solvent: c1ccccc1
Product: Cc1ccc(S(=O)(=O)NC(=O)N2CC(COc3ccccc3)OC2(C)C)cc1

Procedure:
To 20.7 milliliters of 2,2-dimethyl-5-phenoxymethyl oxazolidine, 25 percent w/v in 50 milliliters of benzene was added 419 grams of p-toluene sulfonyl isocyanate. Upon completion of the reaction the solvent, benzene, was removed in vacuo. There was obtained 12.8 grams of the title compound, as a glass. Analytical data supports the structure.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([N+:14]([O-])=O)[CH:11]=[CH:10][C:9]=2[O:17][CH3:18])[CH2:4][CH2:3]1.O.NN>C(O)C.[Ni].O>[CH3:18][O:17][C:9]1[CH:10]=[CH:11][C:12]([NH2:14])=[CH:13][C:8]=1[N:5]1[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]1
Reactant: COc1ccc([N+](=O)[O-])cc1N1CCN(C)CC1
Agent: [Ni]
Agent: NN
Solvent: CCO
Solvent: O
Product: COc1ccc(N)cc1N1CCN(C)CC1
Yield: 53 %

Procedure:
To a solution of the product of step (a) (5.07 g) in ethanol (70 ml) was added a paste of Raney Nickel in water (2 g). To the warmed suspension was added, with constant agitation, hydrazine hydrate (5 ml) dropwise during 20 min with occasional warming. After the main effervescence had ceased, the suspension was heated for 15 min and then filtered with the aid of ethanol under nitrogen. The residues were kept moist and washed with ethanol and the combined filtrate and washings were evaporated to dryness with the aid of ethanol. The dark residue was re-evaporated with ethanol (20 ml), resuspended in ether (40 ml) and the mixture filtered. The residue was washed with ether and dried to give a solid consisting of the title compound (2.365 g) T.l.c System A (70:8:1), Rf 0.25.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CS(C)=O.Cl[C:20]1[C:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH3:33])[N:27]=2)=[CH:24][CH:23]=[CH:22][N:21]=1>O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:20]2[C:25]([C:26]3[CH:31]=[CH:30][N:29]=[C:28]([NH:32][CH3:33])[N:27]=3)=[CH:24][CH:23]=[CH:22][N:21]=2)=[CH:4][CH:3]=1
Reactant: CNc1nccc(-c2cccnc2Cl)n1
Reactant: Nc1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: CNc1nccc(-c2cccnc2Sc2ccc(N)cc2)n1
Temperature: 130 °C
Reaction time: 16 h

Procedure:
To 4-aminothiophenol (1.70 g, 13.6 mmol) and Cs2CO3 (8.90 g, 27.2 mmol) was added DMSO (18 mL). The mixture was stirred for 5 minutes at 100° C. before 4-(2-chloropyridin-3-yl)-N-methylpyrimidin-2-amine (3.00 g, 13.6 mmol) was added. The resulting mixture was stirred for 16 hours at 130° C., then diluted with water and the resulting solid filtered. After washing the solid with water and Et2O it was dried under vacuum to yield the desired product as a tan solid. MS m/z=310 [M+1]+. Calc'd for C16H15N3S: 309.40.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[N:12]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([O:25]C)=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:11]([CH3:27])[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([Cl:28])[CH:9]=3)[C:4]=2[CH:3]=1.C1CCCCC=1.B(Br)(Br)Br.ClCCl>>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[N:12]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:11]([CH3:27])[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([Cl:28])[CH:9]=3)[C:4]=2[CH:3]=1
Reactant: COc1ccc(S(=O)(=O)N2c3ccc(Br)cc3-c3ccc(Cl)cc3C2C)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: C1=CCCCC1
Product: CC1c2cc(Cl)ccc2-c2cc(Br)ccc2N1S(=O)(=O)c1ccc(O)cc1
Yield: 56.8 %

Procedure:
The title compound was prepared from 2-bromo-8-chloro-5-[(4-methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine (0.6 g, 1.25 mmol), cyclohexene (0.32 mL, 3.13 mmol), and 1.0 M boron tribromide in dichloromethane (7.52 mL, 7.52 mmol) according to the procedure and in the same manner as described in Example 1, step b. The crude product was purified by flash column chromatography on silica gel, eluting with dichloromethane to yield 4-[(2-bromo-8-chloro-6-methylphenanthridin-5(6H)-yl)sulfonyl]phenol (0.33 g, 0.71 mmol, 56%) as a light-yellow solid, m.p. 213-215° C.;
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])=[O:17])[CH2:12][CH2:11]2)[N:3]=1.C(N(C(C)C)CC)(C)C.[NH2:39][C:40]1[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=1>C(#N)C>[CH3:9][NH:8][C:6]1[N:7]=[C:2]([NH:39][C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)[N:3]=[C:4]([N:10]2[CH2:11][CH2:12][CH:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:27])[F:28])=[O:17])[CH2:14][CH2:15]2)[N:5]=1
Reactant: CNc1nc(Cl)nc(N2CCC(C(=O)NCc3ccccc3C(F)(F)F)CC2)n1
Reactant: Nc1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CNc1nc(Nc2ccncc2)nc(N2CCC(C(=O)NCc3ccccc3C(F)(F)F)CC2)n1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
To a solution of 1-[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide (75 mg, 0.18 mmol, 1.0 equiv) and diisopropylethylamine (DIEA, 154 □l, 0.875 mmol, 5.00 equiv) in acetonitrile (3 ml) at room temperature, 4-aminopyridine (43.0 mg, 0.349 mmol, 2.00 equiv) was added. The reaction mixture was heated to 65° C. and stirring was continued overnight. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was dissolved up in 1.5 ml DMSO and purified via reverse-phase HPLC purification to afford the title compound. MS (ES+): m/e 487.1 [M+H]+.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[C:18]([CH3:19])=[C:17]([CH:20]2[S:25][CH2:24][C:23](=[N:26]O)[CH2:22][S:21]2)[N:16]=[CH:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O>O1CCCC1>[CH2:7]([N:14]1[C:18]([CH3:19])=[C:17]([C@H:20]2[S:25][CH2:24][C@H:23]([NH2:26])[CH2:22][S:21]2)[N:16]=[CH:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: Cc1c(C2SCC(=NO)CS2)ncn1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1c([C@H]2SC[C@H](N)CS2)ncn1Cc1ccccc1
Temperature: 70 °C

Procedure:
To a suspension of lithium aluminum hydride (2.9 g., 0.076 mole) in dry tetrahydrofuran (120 ml.) under a nitrogen atmosphere is added dropwise a solution of 2-(1-benzyl-5-methyl-4-imidazolyl)-1,3-dithian-5-one oxime (21.3 g., 0.0668 mole) in dry tetrahydrofuran (130 ml.). After heating at 70° C. for one hour, water (40 ml.) is added cautiously and the mixture is filtered hot. The solvent is evaporated and the residue is chased with ethanol to remove traces of water to give a viscous oil (17.0 g.). Careful chromatography on silica gel by gradient elution with 2-6% methanol/chloroform affords 2.2 g. of the trans isomer and 7.3 g. of the cis isomer as viscous semi-solids.
Reaction SMILES: [NH2:1][CH:2]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=1[F:19])[CH2:3][CH:4]([CH3:10])[C:5]([O:7]CC)=O.[C:20]1([CH3:33])[CH:25]=[CH:24][C:23]([C:26]2[S:27][CH:28]=[C:29]([CH:31]=O)[N:30]=2)=[CH:22][CH:21]=1>>[F:19][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=1[CH:2]1[N:1]([CH2:31][C:29]2[N:30]=[C:26]([C:23]3[CH:24]=[CH:25][C:20]([CH3:33])=[CH:21][CH:22]=3)[S:27][CH:28]=2)[C:5](=[O:7])[CH:4]([CH3:10])[CH2:3]1
Reactant: Cc1ccc(-c2nc(C=O)cs2)cc1
Reactant: CCOC(=O)C(C)CC(N)c1c(F)cccc1OC
Product: COc1cccc(F)c1C1CC(C)C(=O)N1Cc1csc(-c2ccc(C)cc2)n1

Procedure:
Prepared according to the described general procedure 2 (GP2) by reaction of ethyl 4-amino-4-(2-fluoro-6-methoxyphenyl)-2-methylbutanoate with commercially available 2-(p-tolyl)thiazole-4-carbaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.94 min.; [M+H]+: 411.02 g/mol.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[N:7]([C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](Br)=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[O:23]=[C:24]1[CH2:29][CH2:28][C:27]([CH:33]=[CH2:34])([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:7]([CH3:8])[C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](/[CH:34]=[CH:33]/[C:27]3([C:30]([OH:32])=[O:31])[CH2:28][CH2:29][C:24](=[O:23])[CH2:25][CH2:26]3)=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])=[O:22])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@H](c1ccc2ccc(Br)cc2n1)N(C)C(=O)OC(C)(C)C
Reactant: C=CC1(C(=O)O)CCC(=O)CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: C[C@H](c1ccc2ccc(/C=C/C3(C(=O)O)CCC(=O)CC3)cc2n1)N(C)C(=O)OC(C)(C)C
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 94.4 %

Procedure:
A solution of [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-methyl-carbamic acid tert-butyl ester (200 mg, 0.55 mmol), 4-oxo-1-vinyl-cyclohexanecarboxylic acid (138 mg, 0.82 mmol), palladium(II) acetate (25 mg, 0.11 mmol), tri-(o-tolyl)phosphine (50 mg, 0.16 mmol) in anhydrous 1,4-dioxane (2 mL) was treated with triethylamine (267 μL, 1.91 mmol). After stirring at 100° C. under microwave irradiation for 30 minutes, the reaction was cooled to room temperature and the volatiles were removed in vacuo. The residue was partitioned between ethyl acetate and a 5% citric acid solution, the aqueous layer was extracted with ethyl acetate (2 x), the organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 to afford the title compound (235 mg, 94%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.48 (s, 9H), 1.68 (d, J=7.1 Hz, 3H), 2.07-2.22 (m, 2H), 2.44-2.70 (m, 6H), 2.75 (br s, 3H), 5.61 (br s, 1H), 6.68 (ABq, ΔδAB=0.31, JAB=16.3 Hz, 2H), 7.36 (d, J=8.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 1H), 7.75 (d, J=8.5 Hz, 1H), 8.05-8.12 (m, 2H). LCMS (m/z) 453.1 [M+H], Tr=2.48 min.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:8]=[CH:7][C:6]=1Br.[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:8]=[CH:7][C:6]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)Cc1cc(Oc2ccc(C(F)(F)F)cc2CN2CCOC2=O)ccc1Br
Product: COC(=O)Cc1cc(Oc2ccc(C(F)(F)F)cc2CN2CCOC2=O)ccc1-c1ccccc1

Procedure:
Prepared according to the procedure described in Example 7, Step 1, using the following starting materials: {2-bromo-5-[2-(2-oxo-oxazolidin-3-ylmethyl)-4-trifluoromethyl-phenoxy]-phenyl}-acetic acid methyl ester and phenylboronic acid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:15](=[O:16])[NH:14][C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:15](=[O:16])[N:14]([CH2:22][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C(CCl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N[C@H]1COc2ccccc2NC1=O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@H]1COc2ccccc2N(CC(=O)OCc2ccccc2)C1=O
Reaction time: 15 h
Yield: 62.1 %

Procedure:
In 150 ml of N,N-dimethylformamide is dissolved 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one, and 8.7 g of benzyl chloroacetate, 8.7 g of anhydrous potassium carbonate and 1 g of potassium iodide are added to the solution. After stirring for 15 hours, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water and recrystallized from ethyl acetate-hexane to give 11.7 g of benzyl 3(S)-tert-butoxycarbonylamino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate as colorless prisms, melting at 122°-124° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:16]([O:18][CH3:19])=[O:17])[N:7]([C:9]2[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:8]=1)(=[O:3])[CH3:2].[Br:20]Br>O1CCOCC1>[Br:20][CH2:2][C:1]([C:4]1[CH:5]=[C:6]([C:16]([O:18][CH3:19])=[O:17])[N:7]([C:9]2[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:8]=1)=[O:3]
Reactant: COC(=O)c1cc(C(C)=O)cn1-c1ncccc1Cl
Reactant: BrBr
Solvent: C1COCCO1
Product: COC(=O)c1cc(C(=O)CBr)cn1-c1ncccc1Cl

Procedure:
427 mg (1.48 mmol) of methyl 4-acetyl-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate were initially charged in 12 ml of dioxane, and 284 mg (1.78 mmol) of bromine were added dropwise at RT. The mixture was then stirred under reflux for 7 h. The solvent was distilled off under reduced pressure, giving an oil which was directly, without purification, reacted further.
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3]([OH:5])=[O:4].[CH3:7][C:8]([Si:11](Cl)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:10])[CH3:9].N1C=CN=C1>CN(C=O)C>[Si:11]([O:1][C@H:2]([CH3:6])[C:3]([OH:5])=[O:4])([C:8]([CH3:10])([CH3:9])[CH3:7])([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: C[C@@H](O)C(=O)O
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: C[C@@H](O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (2R)-2-hydroxypropanoic acid (5 g) in DMF (20 ml) was added TBDPSCl (33.0 g) and imidazole (16.4 g). The reaction was then stirred overnight at RT. The reaction was partitioned between EtOAc (200 ml) and H2O (200 ml). The organics were recovered and washed with 10% citric acid (200 ml), H2O (200 ml) and finally brine (200 ml). The organics were then collected, dried (MgSO4) before being reduced in vacuo. The residue was dissolved in MeOH (200 ml), cooled in an ice bath and potassium carbonate (6.9 g) in H2O was added. After stirring at room temperature for 6 h the solvent was removed in vacuo and the residue diluted with H2O (100 ml). The pH was then adjusted to pH 4 with 10% citric acid, and the aqueous extracted three times with EtOAc (3×200 ml). The organics were collected dried MgSO4 before reducing in vacuo to give the subtitle compound as a colourless oil. Yield: 7.5 g
Reaction SMILES: [ClH:1].Cl.[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N+:17]([C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH:22]=O)([O-:19])=[O:18].C(N(CC)CC)C.[BH4-].[Na+]>CO>[ClH:1].[ClH:1].[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([NH:16][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N+:17]([O-:19])=[O:18])[CH2:12][CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CO
Product: O=[N+]([O-])c1ccccc1CNC1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.1 %

Procedure:
In this reference example, 5.24 g of 1-benzyl-4-amino-piperidine dihydrochloride, 3.02 g of o-nitrobenzaldehyde, 2.02 g of triethylamine and 30 ml of methanol are mixed and stirred at room temperature for one hour. The resultant solution is cooled with ice and stirred. To the stirred solution, 1 g of sodium borohydride is added little by little over a period of one hour. Then, the mixture is brought back to room temperature and stirred at room temperature for 2 hours. The resultant solution is poured into 200 ml of ice water and extracted with ether. The organic layer is washed with water, dried and concentrated. The oily residue is dissolved in 20 ml of ethanol. The solution is mixed with 10 ml of a solution of 5.7 N hydrochloric acid in ethyl acetate. The white crystals deposited are separated by filtration, washed with 20 ml of ethyl acetate and dried to obtain 5.70 g of a crude product. The crude product is recrystallized from hot ethanol to obtain 2.90 g of the desired product.
Reaction SMILES: [H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][C:9]#[N:10].[CH2:11]([NH:13][C:14]1[C:19]([CH:20]=O)=[CH:18][N:17]=[C:16]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:15]=1)[CH3:12].O>C(OCCO)C>[CH2:11]([N:13]1[C:14]2[N:15]=[C:16]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:17]=[CH:18][C:19]=2[CH:20]=[C:8]([C:4]2[S:3][CH:7]=[CH:6][CH:5]=2)[C:9]1=[NH:10])[CH3:12]
Reactant: N#CCc1cccs1
Reactant: CCNc1nc(Nc2ccccc2)ncc1C=O
Agent: [H-]
Agent: [Na+]
Solvent: CCOCCO
Solvent: O
Product: CCn1c(=N)c(-c2cccs2)cc2cnc(Nc3ccccc3)nc21
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 85.9 %

Procedure:
To a suspension of NaH (60% in mineral oil, 27 mg) in 5 mL of 2-ethoxyethanol was added 2-thiopheneacetonitrile (168 mg, 1.36 mmol). After stirring for 5 minutes at room temperature, 4-ethylamino-2-phenylamino-pyrimidine-5-carbaldehyde (300 mg, 1.24 mmol) was added, and the reaction heated at 120° C. for 2 hours, resulting in a dark brown solution. Upon cooling, the solution was poured into water which caused precipitation. The resulting precipitate was removed by filtration and washed with water. The crude product was purified by flash chromatography, eluting with 5% methanol/methylene chloride, followed by 10% methanol/methylene chloride. Concentration of product fractions yielded 370 mg (85%) of (8-ethyl-7-imino-6-thiophen-2-yl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-phenylamine; mp 204°-205° C.