Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][C:9]=2[O:17][CH3:18])[N:5]=[CH:4][N:3]=1.C(O)(=O)C>CCO.[Fe]>[Cl:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][C:9]=2[O:17][CH3:18])[CH:7]=1
Reactant: COc1cc([N+](=O)[O-])ccc1-c1cc(Cl)ncn1
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Product: COc1cc(N)ccc1-c1cc(Cl)ncn1
Temperature: 80 °C
Yield: 93.9 %

Procedure:
A suspension of 4-chloro-6-(2-methoxy-4-nitrophenyl)pyrimidine (0.6 g, 2.259 mmol) in EtOH (Ratio: 2.000, Volume: 10 mL) was stirred at 80° C. to make most of the material solublized, Acetic Acid 20% (Ratio: 1.000, Volume: 5 mL) and iron powder (0.883 g, 15.81 mmol) were added. The resulting mixture was refluxed for 1 h. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc/1.0 M aqueous NaOH. The aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml), dried over magnesium sulfate, filtered and concentrated. The residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜80%). Desired fractions were collected, concentrated and the residue was triturated with DCM to get 0.5 g (82%) of product as light-yellow solid. LC-MS (M+H)+=236. 1H NMR (400 MHz, CDCl3) δ ppm 3.91 (s, 3H) 4.07 (br. s., 2H, NH2) 6.27 (d, J=2.26 Hz, 1H) 6.40 (dd, J=8.53, 2.26 Hz, 1H) 8.04 (d, J=1.25 Hz, 1H) 8.07 (d, J=8.28 Hz, 1H) 8.91 (d, J=1.25 Hz, 1H).
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=[CH:12][CH2:13][N:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:16][CH2:15]3)=[CH:10][C:5]=2[O:4][C:3]1=[O:27]>C(OCC)(=O)C.[Ni]>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][N:17]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[CH2:18][CH2:19]3)=[CH:10][C:5]=2[O:4][C:3]1=[O:27]
Reactant: Cn1c(=O)oc2cc(C=CCN3CCN(c4ccc(F)cc4)CC3)ccc21
Agent: [Ni]
Solvent: CCOC(C)=O
Product: Cn1c(=O)oc2cc(CCCN3CCN(c4ccc(F)cc4)CC3)ccc21
Temperature: 25 °C

Procedure:
0.01 mole of 3-methyl-6-{3-[4-(4-fluorophenyl)-1-piperazinyl]-1-propenyl}benzoxazolinone is dissolved in ethyl acetate in a 500-cm3 flask equipped with a three-way tap and a magnetic stirrer, and 0.5 g of Raney nickel is then added. The mixture is stirred under a hydrogen atmosphere at room temperature and atmospheric pressure. After the theoretical amount of hydrogen has been absorbed, the reaction medium is filtered and the filtrate is evaporated to dryness on a water bath under vacuum. The residue is crystallized in ethanol.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][NH:20][OH:21])=[C:9]2[CH3:22])=[O:7])=[CH:4][CH:3]=1.[N-:25]=[C:26]=[O:27].[Na+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:25][C:26]([N:20]([OH:21])[CH2:19][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)[N:8]([C:6](=[O:7])[C:5]2[CH:23]=[CH:24][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]=1[CH3:22])=[O:27]
Reactant: [N-]=C=O
Reactant: COc1ccc2c(c1)c(CNO)c(C)n2C(=O)c1ccc(Cl)cc1
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)c(CN(O)C(N)=O)c(C)n2C(=O)c1ccc(Cl)cc1
Yield: 53.3 %

Procedure:
To a suspension of 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine (500 mg, 1.45 mmol) in 30 ml of 1,4-dioxane and 15 ml of water at 0° C. is added sodium isocyanate (104 mg, 1.59 mmol) followed by 1.59 ml (1.59 mmol) of 1N hydrochloric acid. The reaction mixture is diluted with ethyl acetate and washed once with water, and finally with a saturated solution of sodium chloride. It is further dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue is recrystallized from methylene chloride and dried to give 300 mg (53%) of pure N-(aminocarbonyl)-1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine (53%); mp 151.5°-154° C. dec.
Reaction SMILES: [C:1]([C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][C:15]([O-:17])=O)=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:20])#[N:2].[Li+].Cl.[NH2:23][C@H:24]1[CH2:28][CH2:27][N:26]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([OH:39])[CH:37]=3)[CH:32]=[CH:31][CH:30]=2)[C:25]1=[O:40].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][C:15]([NH:23][C@H:24]3[CH2:28][CH2:27][N:26]([C:29]4[C:38]5[C:33](=[CH:34][CH:35]=[C:36]([OH:39])[CH:37]=5)[CH:32]=[CH:31][CH:30]=4)[C:25]3=[O:40])=[O:17])=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:20])#[N:2]
Reactant: N#Cc1ccc(Cn2cncc2CCC(=O)[O-])cc1F
Reactant: N[C@H]1CCN(c2cccc3ccc(O)cc23)C1=O
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1ccc(Cn2cncc2CCC(=O)N[C@H]2CCN(c3cccc4ccc(O)cc34)C2=O)cc1F

Procedure:
A mixture of lithium 3-[1-(4-cyano-3-fluorobenzyl)-1H-imidazol-5-yl]propionate, as described above in Step E (55 mg, 0.20 mmol), (S)-3-amino-1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidine hydrochloride, as described in Example 9A, (56 mg, 0.20 mmol), PYBOP (105 mg, 0.20 mmol), and N,N-diisopropylethylamine (0.075 mL, 0.43 mmol) was stirred in DMF (0.5 mL) at ambient temperature for 4 hours. The reaction mixture was partitioned between saturated aqueous NaHCO3 (5 mL) and CHCl3 (10 mL). The aqueous layer was extracted further with CHCl3 (2×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2—1% MeOH—0.1% NH4OH to CH2Cl2—8% MeOH—0.8% NH4OH to yield the titled product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[C:4]([F:20])[CH:3]=1.[C:21]([NH:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)(=[O:23])[CH3:22].C(=O)([O-])O.[Na+]>O1CCOCC1.O.C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:29]2[CH:30]=[C:25]([NH:24][C:21](=[O:23])[CH3:22])[CH:26]=[CH:27][CH:28]=2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[C:4]([F:20])[CH:3]=1
Reactant: Cn1cc(C(=O)/C=C/c2ccc(Cl)cc2F)ccc1=O
Reactant: CC(=O)Nc1cccc(B(O)O)c1
Agent: [Rh]
Agent: C1=C\CC/C=C\CC/1
Agent: O=C([O-])O
Solvent: O
Solvent: C1COCCO1
Solvent: C1=CCCC=CCC1
Product: CC(=O)Nc1cccc(C(CC(=O)c2ccc(=O)n(C)c2)c2ccc(Cl)cc2F)c1

Procedure:
In analogy to example 203, step 1, (E)-5-(3-(4-chloro-2-fluorophenyl)acryloyl)-1-methylpyridin-2(1H)-one (example 319, step 2) was reacted with 3-acetamidophenylboronic acid in the presence of chloro(1,5-cyclooctadiene)rhodium(I) dimer and sodium hydrogencarbonate in 1,4-dioxane and water at 60° C. to give the title compound as a brown solid, MS (ESI+): m/z=427.1 [M+H]+.
Reaction SMILES: [NH:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[N:3]=[CH:2]1.[C:10]([OH:15])(=[O:14])[C:11]([OH:13])=[O:12].[C:16]1([CH:22]([CH2:25][CH3:26])[CH2:23][OH:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[C:10]([OH:15])(=[O:14])[C:11]([OH:13])=[O:12].[C:16]1([CH:22]([CH2:25][CH3:26])[CH2:23][O:24][C:11]([N:6]2[CH2:7][CH2:8][C:9]3[NH:1][CH:2]=[N:3][C:4]=3[CH2:5]2)=[O:12])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: c1nc2c([nH]1)CCNC2
Reactant: CCC(CO)c1ccccc1
Agent: O=C(O)C(=O)O
Product: CCC(COC(=O)N1CCc2[nH]cnc2C1)c1ccccc1

Procedure:
The compound was prepared from 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine and 2-phenyl-1-butanol oxalate.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH:13]([CH:21]=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[CH3:24][O:25][CH2:26][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(NC(=O)[C@H](C)C[C@H](O)[C@@H](NC(OC(C)(C)C)=O)CC(C)(C)CC(N1C2C(=CC=CC=2)CC(COCC=C)C1)=O)CCC>>[CH2:1]([O:8][C:9]([N:11]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH:13]([CH:21]=[CH:24][O:25][CH3:26])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=CC1CN(C(=O)OCc2ccccc2)c2ccccc2O1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C=CCOCC1Cc2ccccc2N(C(=O)CC(C)(C)C[C@H](NC(=O)OC(C)(C)C)[C@@H](O)C[C@@H](C)C(=O)NCCCC)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Product: COC=CC1CN(C(=O)OCc2ccccc2)c2ccccc2O1

Procedure:
The title compound is prepared analogously to the process described in Example 138b) starting from 1.25 g of N-benzyloxycarbonyl-2(R,S)-formyl-3,4-dihydro-2H-1,4-benzoxazine (Example 107), 7.2 g of methoxymethyl-triphenylphosphonium chloride and 1.57 g of potassium bis(trimethylsilyl)amide: Rf (A)=0.49 und 0.54.
Reaction SMILES: [Br:1][CH:2]=[CH:3][CH:4]=[C:5]([CH3:9])[CH2:6][CH:7]=[O:8].CCCCC.C(N(CC)CC)C.Br[Si:23]([CH3:26])([CH3:25])[CH3:24]>C(#N)C>[Br:1][CH:2]=[CH:3][CH:4]=[C:5]([CH3:9])[CH:6]=[CH:7][O:8][Si:23]([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(=CC=CBr)CC=O
Reactant: C[Si](C)(C)Br
Solvent: CCN(CC)CC
Solvent: CCCCC
Solvent: CC#N
Product: CC(C=CO[Si](C)(C)C)=CC=CBr
Temperature: 0 °C
Reaction time: 48 h
Yield: 40.6 %

Procedure:
6-Bromo-3-methyl-3,5-hexadienal (0.95 g; 5 mmol) dissolved in acetonitrile (25 cc) and pentane (25 cc) is introduced, under an argon atmosphere, into a 100-cc round flask fitted with a septum and a magnetic stirrer. Triethylamine (1 g; 10 mmol, i.e. 2 equivalents) is then added. After the mixture has been cooled to 0° C., bromotrimethylsilane (1.53 g; 2 equivalents) is added dropwise. The temperature is allowed to return to about 20° C. After 48 hours the reaction is complete. The acetonitrile phase is extracted with pentane (4×15 cc) under an argon atmosphere. After evaporation of the solvent and distillation, 6-bromo-3-methyl-1-trimethylsilyloxy-1,3,5-hexatriene (0.53 g) is obtained (b.p. 0.06 kPa=92°-95° C.). The yield is 46.8%. The structure of the product obtained is confirmed by the infrared spectrum and the proton nuclear magnetic resonance spectrum.
Reaction SMILES: [CH3:1][N:2]1[C:6]([O:7][CH:8]2[CH2:11][O:10][CH2:9]2)=[C:5]([CH2:12]O)[C:4]([C:14]([F:17])([F:16])[F:15])=[N:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:38]>ClCCl>[Br:38][CH2:12][C:5]1[C:4]([C:14]([F:17])([F:16])[F:15])=[N:3][N:2]([CH3:1])[C:6]=1[O:7][CH:8]1[CH2:11][O:10][CH2:9]1
Reactant: Cn1nc(C(F)(F)F)c(CO)c1OC1COC1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cn1nc(C(F)(F)F)c(CBr)c1OC1COC1
Reaction time: 2 h
Yield: 103.2 %

Procedure:
[1-Methyl-5-(oxetan-3-yloxy)-3-trifluoromethyl-1H-pyrazol-4-yl]-methanol (8.14 g, 32.3 mmol) was dissolved in dichloromethane (100 ml) and triphenyl phosphine (8.96 g, 34.2 mmol) and carbon tetrabromide (10.31 g, 31.05 mmol) were added. The solution was stirred for 2 hours and concentrated to give an orange oil. Purification by chromatography on silica gel (eluent: ethyl acetate/hexane) yielded the product as an orange oil (10.1 g) which was used in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH:14]=2)=[CH:5][CH:4]=1.CN([CH2:18][C:19]1[C:27]2[C:22](=[N:23][CH:24]=[CH:25][CH:26]=2)[NH:21][CH:20]=1)C>CC(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH2:14][CH2:13][N:12]([CH2:18][C:19]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[CH2:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(C2=CCNCC2)cc1
Reactant: CN(C)Cc1c[nH]c2ncccc12
Solvent: CC(C)O
Product: COc1ccc(C2=CCN(Cc3c[nH]c4ncccc34)CC2)cc1
Yield: 41 %

Procedure:
4-(4-Methoxyphenyl)-1,2,3,6-tetrahydropyridine (540 mg, 2.8 mmol) was reacted with 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (500 mg, 2.8 mmol) as in Example 4 to give the title compound (367 mg, 41%) as tan crystals, m.p. 202°-204° C. (iPrOH); (Found: C, 73.51; H, 6.74; N, 12.15. C20H21N3O.0.33 H2O.0.2 C3 H8O requires C, 73.34; H, 6.95; N, 12.45%); δH (DMSO-d6) 2.44 (2H, m, tetrahydropyridinyl CH2), 2.70 (2H, m, tetrahydropyridinyl CH2), 3.10 (2H, m, tetrahydropyridinyl CH2), 3.74 (3H, s, ArOCH3), 3.76 (2H, s, ArCH2N), 6.04 (1H, m, CH=CR), 6.90 (2H, d, J 8.6 Hz, ArH), 7.04 (1H, dd, J 7.7, 4.6 Hz, 5-H), 7.36 (2H, d, J 8.5 Hz, ArH), 7.40 (1H, s, 2-H), 8.06 (1H, d, J 7.7 Hz, 4-H), 8.20 (1H, d, J 4.6 Hz, 6-H), and 11.48 (1H, br s, NH); m/z (CI+, NH3) 320 (M+1)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][Si](C)(C)C)[C:5]([NH2:8])=[N:6][CH:7]=1.[F-].[K+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[CH:10])[C:5]([NH2:8])=[N:6][CH:7]=1
Reactant: C[Si](C)(C)C#Cc1cc(Cl)cnc1N
Agent: [F-]
Agent: [K+]
Solvent: CO
Product: C#Cc1cc(Cl)cnc1N
Yield: 89.3 %

Procedure:
A suspension of 1.6 g of 5-chloro-3-trimethylsilanylethynylpyridin-2-ylamine and 1.24 g of potassium fluoride in 80 ml of methanol is brought to reflux for approximately 3 hours 30 minutes. After returning to a temperature in the region of 20° C., the mixture is filtered through celite, and the insoluble material is washed three times with 50 ml of methanol. The filtrate is concentrated to dryness under reduced pressure (13 kPa). The residue is taken up with 100 ml of dichloromethane. The solution obtained is washed with three times 60 ml of water, dried over magnesium sulfate, filtered, and concentrated to dryness under reduced pressure (13 kPa). 0.97 g of 5-chloro-3-ethynylpyridin-2-ylamine is thus obtained in the form of a solid, the characteristics of which are as follows:
Reaction SMILES: Br[C:2]1[S:3][C:4]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[C:5]([C:7](=[O:29])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:28])[C:13]=2[N:14]2[CH2:20][CH2:19][CH2:18][C@H:17]([NH:21][C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:16][CH2:15]2)[N:6]=1.[F:38][C:39]1[CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:42]=[CH:41][N:40]=1.CC([O-])=O.[K+].C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[F:38][C:39]1[CH:44]=[C:43]([C:2]2[S:3][C:4]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[C:5]([C:7](=[O:29])[NH:8][C:9]3[CH:10]=[N:11][N:12]([CH3:28])[C:13]=3[N:14]3[CH2:20][CH2:19][CH2:18][C@H:17]([NH:21][C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:16][CH2:15]3)[N:6]=2)[CH:42]=[CH:41][N:40]=1
Reactant: Cn1ncc(NC(=O)c2nc(Br)sc2NC(=O)OC(C)(C)C)c1N1CCC[C@H](NC(=O)C(F)(F)F)CC1
Reactant: CC1(C)OB(c2ccnc(F)c2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: CC(=O)[O-]
Solvent: CC#N
Product: Cn1ncc(NC(=O)c2nc(-c3ccnc(F)c3)sc2NC(=O)OC(C)(C)C)c1N1CCC[C@H](NC(=O)C(F)(F)F)CC1
Yield: 59.8 %

Procedure:
In a microwave reaction vial, tert-butyl N-[2-bromo-4-[[1-methyl-5-[(4S)-4-[(2,2,2-trifluoroacetyl)amino]azepan-1-yl]pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (100 mg, 0.16 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (110 mg, 0.49 mmol) and PD(DPPF)CL2 (12 mg, 0.016 mmol) were dissolved in acetonitrile (3 mL). 1.0M KOAc (0.25 mL, 0.25 mmol) and 1.0M Na2CO3 (0.25 mL, 0.25 mmol) were added and the reaction was irradiated with microwave at 120° C. for 30 min. The mixture was cooled, filtered through Celite, concentrated and purified via flash chromatography, EA/heptane 0% to 100% to afford tert-butyl N-[2-(2-fluoro-4-pyridyl)-4-[[1-methyl-5-[(4S)-4-[(2,2,2-trifluoroacetyl)amino]azepan-1-yl]pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (60 mg, 58%). This compound was stirred with 4N HCl in dioxane (3 mL, 12 mmol) and methanol (2 mL) at room temperature for 3 h. Solvent was removed under reduced pressure. The residue was dissolved in methanol (3 mL) and water (1 mL), potassium carbonate (67 mg, 0.48 mmol) was added and the mixture was heated at 60° C. for 1.5 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EA 3×. The combined organic layers were dried over MgSO4 and the solvent removed under reduced pressure and the residue purified by preparative HPLC to afford 417. 1H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 8.29 (d, J=5.3 Hz, 1H), 7.74 (d, J=5.3 Hz, 3H), 7.59 (s, 1H), 7.42 (s, 1H), 3.66 (s, 3H), 3.24-3.01 (m, 5H), 1.94-1.73 (m, 3H), 1.67-1.48 (m, 3H). LCMS (ES+) m/z 431 (M+1)
Reaction SMILES: Br[CH2:2][C:3](=[O:16])[C:4]([C:7]1[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=1)[C:12]#[N:13])([CH3:6])[CH3:5].[N-:17]=[N+:18]=[N-:19].[Na+]>CN(C=O)C.O>[N:17]([CH2:2][C:3](=[O:16])[C:4]([C:7]1[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=1)[C:12]#[N:13])([CH3:6])[CH3:5])=[N+:18]=[N-:19]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C(=O)CBr)c1ccc(F)c(C#N)c1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C(=O)CN=[N+]=[N-])c1ccc(F)c(C#N)c1
Reaction time: 2 h
Yield: 76.1 %

Procedure:
To a stirred solution of 5-(4-bromo-2-methyl-3-oxobutan-2-yl)-2-fluorobenzonitrile (10 g, 35.2 mmol) in DMF (100 mL) at 0° C. was added NaN3 (2.52 g, 38.7 mmol, 1.1 eq) portionwise. After stirring 2 h, the residue was diluted with water and extracted with EtOAc. The combined extracts were washed with brine (100 mL), dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography (silica, Hex/EtOAc=4:1) to give 5-(4-azido-2-methyl-3-oxobutan-2-yl)-2-fluorobenzonitrile (6.6 g, 2 step overall yield 78%). 1H NMR (400 MHz, CDCl3) δ 7.57-7.55 (m, 1H), 7.50-7.46 (m, 1H), 7.25 (t, J=7.2 Hz, 1H), 3.8 (s, 2H), 1.55 (s, 6H).
Reaction SMILES: [OH:1]O.[CH3:3][S:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:10][CH2:9][C:8]1=[O:25].O.N>C(O)(=O)C>[CH3:3][S:4]([CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:10][CH2:9][C:8]1=[O:25])=[O:1]
Reactant: CSCCN1C(=O)CN=C(c2ccccc2)c2cc(Cl)ccc21
Reactant: OO
Agent: N
Solvent: CC(=O)O
Solvent: O
Product: CS(=O)CCN1C(=O)CN=C(c2ccccc2)c2cc(Cl)ccc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 10 ml of 15% aqueous hydrogen peroxide is added with ice-cooling to a mixture of 1.5 g of 1-(β-methylthioethyl)-5-phenyl-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one and 20 ml of acetic acid. The resultant mixture is stirred at 0° C for 30 minutes and then at room temperature for 1 hour. The reaction mixture is poured into ice water, basified with ammonia water and extracted with chloroform. The chloroform extracts are combined, dried over anhydrous sodium sulfate, and the solvent is removed under reduced pressure. The residue is allowed to stand to form crystals. Recrystallization from ethylacetate gives 1-(β-methylsulfinylethyl)-5-phenyl-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one, m.p. 166° - 167° C.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)[CH3:3].[CH:18]1([C:21](Cl)=[O:22])[CH2:20][CH2:19]1.C(N(CC)CC)C>>[CH:18]1([C:21]([O:17][C@H:14]2[CH2:15][CH2:16][C@H:11]([C:8]3[CH:9]=[CH:10][C:5]([CH2:4][N:2]([CH3:1])[CH3:3])=[CH:6][CH:7]=3)[CH2:12][CH2:13]2)=[O:22])[CH2:20][CH2:19]1
Reactant: O=C(Cl)C1CC1
Reactant: CN(C)Cc1ccc([C@H]2CC[C@H](O)CC2)cc1
Solvent: CCN(CC)CC
Product: CN(C)Cc1ccc([C@H]2CC[C@H](OC(=O)C3CC3)CC2)cc1

Procedure:
from trans-4-(4-dimethylaminomethylphenyl)-cyclohexanol and cyclopropane carboxylic acid chloride/triethylamine. Colourless wax.
Reaction SMILES: I[CH:2](I)[CH3:3].C(=O)([O-])[O-].[K+].[K+].[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[C:20]([F:23])[C:21]=1[F:22])[N:18]=[C:17]([SH:24])[C:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:15]2[OH:30]>CN(C)C=O>[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[C:20]([F:23])[C:21]=1[F:22])[N:18]1[CH:2]([CH3:3])[S:24][C:17]1=[C:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:15]2=[O:30]
Reactant: CCOC(=O)c1c(S)nc2c(F)c(F)c(F)cc2c1O
Reactant: CC(I)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c2n(c3c(F)c(F)c(F)cc3c1=O)C(C)S2
Reaction time: 0.5 h
Yield: 50.8 %

Procedure:
To 25 ml of N,N-dimethylformamide were added 12 g of diiodoethane and 8.3 g of potassium carbonate, a solution of 6.07 g of the compound obtained in Example 4 dissolved in 60 ml of N,N-dimethylformamide was gradually dropped thereinto, and the mixture was stirred for 30 minutes at the same temperature. N,N-Dimethylformamide was evaporated therefrom in vacuo, the residue was dissolved in a mixture of chloroform and methanol (2:1), washed with water, dried over magnesium sulfate, the solvent was evaporated therefrom, and the crystals separated out therefrom were washed with ether to give 3.35 g of ethyl 6,7,8-trifluoro-1-methyl-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate.
Reaction SMILES: [CH3:1][C:2]1([CH3:37])[O:7][C:6]2[CH:8]=[CH:9][C:10]([CH:12]([OH:36])[CH2:13][NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]3[CH:27]=[C:28]([S:32]([NH2:35])(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=3)=[CH:11][C:5]=2[CH2:4][O:3]1>C(O)C.CCCCCCC>[CH3:1][C:2]1([CH3:37])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@H:12]([OH:36])[CH2:13][NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]3[CH:27]=[C:28]([S:32]([NH2:35])(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=3)=[CH:11][C:5]=2[CH2:4][O:3]1
Reactant: CC1(C)OCc2cc(C(O)CNCCCCCCOCCCCc3cccc(S(N)(=O)=O)c3)ccc2O1
Solvent: CCO
Solvent: CCCCCCC
Product: CC1(C)OCc2cc([C@H](O)CNCCCCCCOCCCCc3cccc(S(N)(=O)=O)c3)ccc2O1
Yield: 23.8 %

Procedure:
Resolution of 3-{4-[(6-{[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}hexyl)oxy]butyl}benzenesulfonamide (0.403 g) on an HPLC Chiralcel OJ column using 40% ethanol/heptane afforded the title compound (0.096 g).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25](B(O)O)[CH:26]=4)[C:21]([CH3:32])([CH3:31])[CH2:20]3)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.Cl[C:34]1[N:42]=[CH:41][N:40]=[C:39]2[C:35]=1[NH:36][CH:37]=[N:38]2.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:32][C:21]1([CH3:31])[C:22]2=[N:23][CH:24]=[C:25]([C:34]3[N:42]=[CH:41][N:40]=[C:39]4[C:35]=3[N:36]=[CH:37][NH:38]4)[CH:26]=[C:27]2[N:19]([C:6]2[C:5]3[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:7]=2[CH3:18])[CH2:20]1
Reactant: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(B(O)O)cc21
Reactant: Clc1ncnc2nc[nH]c12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(-c3ncnc4[nH]cnc34)cc21
Temperature: 120 °C

Procedure:
Prepared according to procedure P using 1-(7-fluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid (25 mg, 0.058 mmol), 6-chloropurine (9 mg, 0.058 mmol), PdCl2(PPh3)2 (4.1 mg, 0.0058 mmol), sodium carbonate (12.3 mg, 0.117 mmol) and heating in the microwave for 1 h at 120° C. After purification 4-(3,3-dimethyl-6-(9H-purin-6-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-pyridinyl)quinoline was obtained as a yellow film. 1H NMR (400 MHz, MeOH) δ ppm 9.27 (1H, br. s.), 8.83 (1H, s), 8.67-8.73 (1H, m), 8.41 (1H, br. s.), 8.01-8.12 (2H, m), 7.92 (1H, d, J=7.8 Hz), 7.83 (1H, dd, J=10.0, 2.5 Hz), 7.52-7.60 (2H, m), 7.48 (1H, ddd, J=9.3, 8.3, 2.5 Hz), 4.06-4.12 (1H, m), 3.95-4.03 (1H, m), 2.33 (3H, s), 1.70 (3H, s), 1.62 (3H, s). Mass Spectrum (ESI) m/e=503 (M+1).