Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:11]([CH2:12][CH:13]=[CH:14][OH:15])=[C:10]([Cl:16])[N:9]=[C:8]2[CH2:17][CH2:18][CH2:19][CH3:20])=[CH:4][CH:3]=1.[C:23]1(=[O:33])[O:28][C:26](=[O:27])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]12>C(Cl)(Cl)Cl.CCOCC>[C:26]([C:25]1[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=1[C:23]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:11]([CH2:12][CH:13]=[CH:14][OH:15])=[C:10]([Cl:16])[N:9]=[C:8]2[CH2:17][CH2:18][CH2:19][CH3:20])=[CH:21][CH:22]=1)=[O:33])([OH:28])=[O:27]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: CCCCc1nc(Cl)c(CC=CO)n1Cc1ccc(N)cc1
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: CCCCc1nc(Cl)c(CC=CO)n1Cc1ccc(NC(=O)c2ccccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 95 mg of 3-[1-(4-aminobenzyl)-2-butyl-4-chloroimidazol-5-yl]propen-1-ol in 2 mL of CHCl3 was added 45 mg of phthalic anhydride and the mixture was stirred at room temperature for 1 hour. During this period of time the initially clear solution became turbid and produced solid. The reaction mixture was diluted with 2 mL of ether and the solid was collected by filtration and washed with ether. The desired product was obtained as a tan solid, 115 mg, m.p. 150°-151°; NMR (10% DMSO-d6 /CDCl3): δ 9.94 (s, 1h); 7.71 and 6.93 (d, 4H, J=8.3 Hz); 6.36 (m, 2H); 5.1 (s, 2H); 4.18 (d, 2H, J=3.9 Hz); 2.6 (t, 3H, J=7.4 Hz); 1.68 (m, 2H); 1.34 (m, 2H); 0.89 (t, 3H, J=7.4 Hz).
Reaction SMILES: [C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].[I:18]I.CO>C(Cl)(Cl)Cl.[N+]([O-])(O)=O>[I:18][C:16]1[C:14](=[O:15])[NH:13][C:11](=[O:12])[N:10]([CH:17]=1)[C@@H:1]1[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3]
Reactant: II
Reactant: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Solvent: CO
Solvent: O=[N+]([O-])O
Solvent: ClC(Cl)Cl
Product: O=c1[nH]c(=O)n([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1I
Temperature: 80 °C

Procedure:
In a round bottom flask, uridine (1 g, 4.1 mmol) and iodine powder (1.15 g, 4.5 mmol) were dissolved in a mixture of CHCl3 (55 ml) and 1M HNO3 (10 ml). The reaction was heated at reflux (80° C.) for 5 h. Reaction progress was monitored by TLC (30% methanol in chloroform, Rf: 0.60; RfSM: 0.45). Upon cooling of the reaction mixture to 4° C., crystals of the title compound formed as colourless needles. The precipitate was collected by filtration and dried under vacuum overnight to provide 1.39 g (92%) of 5-iodouridine 1; δH (DMSO-d6, 300 MHz) 3.49-3.71 (2H, m, H-5′), 3.84-3.88 (1H, m, H-4′), 3.98 (1H, t, J=5.0 Hz, H-3′), 4.02 (1H, t, J=5.0 Hz, H-2′), 5.08 (1H, d, J=5.3 Hz, OH-3′), 5.27 (1H, t, J=4.7 Hz, OH-5′), 5.43 (1H, d, J=5.4 Hz, OH-2′), 5.71 (1H, d, J=4.6 Hz, H-1′), 8.48 (1H, s, H-6) 11.69 (1H, s, NH); δC (DMSO-d6, 300 MHz) 61.2 (C-5′), 70.3 (C-3′), 70.9 (C-5), 75.0 (C-2′), 85.7 (C-4′), 89.5 (C-1′), 146.0 (C-6), 152.5 (C-2), 162.9 (C-4). m/z (ESI) 388.0000 [M+NH4]+, C9H15IN3O6 requires 388.0000.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][N:28]=[C:4]2[N:3]1[CH:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1.[CH2:36]([Mg]Br)[CH:37]=[CH2:38].[Cl-].[NH4+]>O1CCCC1>[OH:35][C:32]1([CH2:38][CH:37]=[CH2:36])[CH2:31][CH2:30][CH:29]([N:3]2[C:2](=[O:1])[C:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]3[N:26]=[CH:27][N:28]=[C:4]23)[CH2:34][CH2:33]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2CCC(=O)CC2)c2ncnn12
Reactant: C=CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C=CCC1(O)CCC(n2c(=O)c(Cc3ccc(-c4ccccc4C#N)cc3)c(CCC)n3ncnc23)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 30 %

Procedure:
4′-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.8 g) was dissolved in tetrahydrofuran (10 mL), and allylmagnesium bromide (1.0 M diethyl ether solution, 2.1 mL) was added at −78° C. The reaction mixture was warmed to room temperature, and the mixture was stirred for 16 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.26 g, 30%).
Reaction SMILES: C1COCC1.[CH3:6][O:7][C:8]1[C@:15]2([CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[C:16](=[O:17])[C@@H:11]([C@:12]([CH3:42])([CH2:28][CH2:29][CH2:30][C:31]([CH3:41])([O:33][Si:34]([CH2:39][CH3:40])([CH2:37][CH3:38])[CH2:35][CH3:36])[CH3:32])[C@@H:13]([CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[CH2:14]2)[C:10](=[O:43])[C:9]=1[Si:44]([CH3:47])([CH3:46])[CH3:45].[Li]N1C(C)(C)CCCC1(C)C.[C:59](Cl)(=[O:63])[CH:60]([CH3:62])[CH3:61]>CCOC(C)=O.CCCCCC>[C:59]([C@:11]12[C:16](=[O:17])[C@:15]([CH2:18][CH:19]=[C:20]([CH3:21])[CH3:22])([CH2:14][C@H:13]([CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[C@@:12]1([CH3:42])[CH2:28][CH2:29][CH2:30][C:31]([CH3:41])([O:33][Si:34]([CH2:35][CH3:36])([CH2:37][CH3:38])[CH2:39][CH3:40])[CH3:32])[C:8]([O:7][CH3:6])=[C:9]([Si:44]([CH3:47])([CH3:46])[CH3:45])[C:10]2=[O:43])(=[O:63])[CH:60]([CH3:62])[CH3:61]
Reactant: CC[Si](CC)(CC)OC(C)(C)CCC[C@]1(C)[C@@H](CC=C(C)C)C[C@@]2(CC=C(C)C)C(=O)[C@@H]1C(=O)C([Si](C)(C)C)=C2OC
Reactant: CC(C)C(=O)Cl
Agent: [Li]N1C(C)(C)CCCC1(C)C
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)OC(C)(C)CCC[C@]1(C)[C@@H](CC=C(C)C)C[C@@]2(CC=C(C)C)C(=O)[C@]1(C(=O)C(C)C)C(=O)C([Si](C)(C)C)=C2OC
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 23.6 %

Procedure:
A THF (0.5 mL) solution of 45 (7.0 mg, 11 μmol, 1 equiv.) was cooled to −78° C. in a 10-mL test tube, and a freshly prepared THF solution of lithium tetramethylpiperidide (0.50 M, 113 μL, 57 μmol, 5 equiv.) was added dropwise. The resulting yellow-orange solution was stirred at −78° C. for 10 min and at 0° C. for 10 min. The solution was then cooled to −78° C., and isobutyryl chloride (6.0 μL, 57 μmol, 5 equiv.) was added. The resulting yellow solution was stirred at −78° C. for 50 min, was slowly warmed to 0° C. over 50 min, and subsequently quenched with saturated aqueous NaHCO3. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a yellow residue. Preparatory thin-layer chromatography (3×98:2 hexane:EtOAc) afforded 1.8 mg (2.6 μmol, 24% yield) of 46 as a colorless residue along with 1.7 mg (2.8 μmol, 25% recovery) of 45. TLC Rf 0.47 (95:5 hexane:EtOAc). 1H-NMR (600 MHz; CDCl3): δ 5.00-4.96 (m, 2H), 3.90 (s, 3H), 2.55 (dd, J=14.6, 6.4 Hz, 1H), 2.41 (dd, J=14.5, 7.7 Hz, 1H), 2.08 (d, J=15.0 Hz, 1H), 1.97 (septet, J=6.5 Hz, 1H), 1.92-1.85 (m, 2H), 1.79-1.72 (m, 1H), 1.68 (s, 3H), 1.66 (s, 3H), 1.57-1.56 (m, 3H), 1.55-1.53 (m, 3H), 1.50-1.42 (m, 2H), 1.39-1.31 (m, 3H), 1.30-1.24 (m, 2H), 1.17 (s, 3H), 1.17 (s, 3H), 1.13 (d, J=6.5 Hz, 3H), 1.02 (d, J=6.5 Hz, 3H), 0.98 (s, 3H), 0.92 (t, J=7.9 Hz, 9H), 0.54 (q, J=7.9 Hz, 6H), 0.26 (s, 9H). HRMS-ESI (m/z): [M+Na]+ calculated for C40H70O5Si2, 709.4654. found, 709.4626.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.C([NH:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])[CH2:35][S:34][C:33]1=[O:38])(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.N1CCCCC1.NCCN1C(=O)/C(=C/C2C=CC=CC=2)/SC1=O>>[NH2:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])/[C:35](=[CH:4]/[C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=2[OH:1])/[S:34][C:33]1=[O:38]
Reactant: O=C1CSC(=O)N1CCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccccc1O
Agent: NCCN1C(=O)S/C(=C\c2ccccc2)C1=O
Solvent: C1CCNCC1
Product: NCCN1C(=O)S/C(=C\c2ccccc2O)C1=O

Procedure:
The title compound 30i was prepared from 2-hydroxybenzaldehyde (76 mg, 0.62 mmol), compound 29 (250 mg, 0.62 mmol) and piperidine (20.0 μL, 0.19 mmol) in a manner similar to that described for 30a in 50.0% (117 mg) yield as a yellow solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]([C:9]2[O:10][C:11]3[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14](Br)[C:12]=3[CH:13]=2)=[O:8])=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[O:47]1[CH2:51]CCC1.[OH2:52]>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[Pd]Cl>[CH3:19][O:18][C:17]1[CH:16]=[CH:15][C:14]([C:51]([OH:47])=[O:52])=[C:12]2[C:11]=1[O:10][C:9]([C:7]([C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[O:8])=[CH:13]2
Reactant: C1CCOC1
Reactant: O
Reactant: COc1ccc(Br)c2cc(C(=O)c3ccncc3)oc12
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)O)c2cc(C(=O)c3ccncc3)oc12
Temperature: 80 °C
Reaction time: 72 h

Procedure:
2-[(Pyridin-4-yl)carbonyl]-4-bromo-7-methoxybenzofuran (3.3 g), triphenylphosphine (1 g), bis(triphenylphosphine)palladium (II) chloride (0.47 g), triethylamine (14 ml), tetrahydrofuran (150 ml) and H2O (57 ml) were combined in a Parr pressure reactor. The vessel was purged with carbon monoxide, charge to 180 psi with carbon monoxide and then heated to 80° C. with stirring for 3 days. On cooling and release of pressure the tetrahydrofuran was removed in vacuo. The remaining aqueous mixture was basified to pH14 with 1N sodium hydroxide solution (250 ml) and washed with ethyl acetate (200 ml). The aqueous layer was then acidified to pH5 with acidic acid under ice bath cooling. The resulting precipitate was collected by filtration and dried to give a beige solid (2.97 g). M.S. M+H observed
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[C:5]([C:10]#[N:11])=[C:4]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.C1(C2[O:25]N2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>ClCCl>[NH2:1][C:2]1[N:7]=[C:6]([S:8]([CH3:9])=[O:25])[C:5]([C:10]#[N:11])=[C:4]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1
Reactant: CSc1nc(N)nc(-c2cccs2)c1C#N
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Solvent: ClCCl
Product: CS(=O)c1nc(N)nc(-c2cccs2)c1C#N
Reaction time: 16 h
Yield: 54.4 %

Procedure:
To a stirred suspension of 2.65 g (10.7 mmol) 2-amino-4-(methylthio)-6-(2-thienyl)-pyrimidine-5-carbonitrile in 200 ml dichloromethane was added 2.79 g (10.7 mmol) 3-phenyl-2-(phenylsulfonyl)oxaziridine and stirring continued for 16 hours at room temperature. The resulting crystals were collected by filtration and washed with 30 ml dichloromethane to afford 1.54 g (55%) 2-amino-4-methanesulfinyl-6-thiophen-2-yl-pyrimidine-5-carbonitrile as a white crystalline solid. EI-MS m/e (%): 264 (M+, 20), 218 (32), 201 (20), 159 (100).
Reaction SMILES: COC(=O)[CH:4](Br)[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][CH2:13][CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:19]=2[CH3:20])=[N:10][CH:11]=1.[NH2:29][C:30]([NH2:32])=[S:31].C([O-])(=[O:35])C.[Na+].C([O-])(O)=O.[Na+]>CCOCC.C(O)C>[NH:29]=[C:30]1[NH:32][C:4](=[O:35])[CH:5]([C:6]2[CH:7]=[CH:8][C:9]([O:12][CH2:13][CH2:14][C:15]3[N:16]=[C:17]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[O:18][C:19]=3[CH3:20])=[N:10][CH:11]=2)[S:31]1
Reactant: CC(=O)[O-]
Reactant: COC(=O)C(Br)Cc1ccc(OCCc2nc(-c3ccccc3)oc2C)nc1
Reactant: NC(N)=S
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOCC
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(C2SC(=N)NC2=O)cn1
Yield: 90.7 %

Procedure:
A mixture of 2-bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionic acid methyl ester (1.07 g), thiourea (0.2 g), sodium acetate (0.22 g) and ethanol (25 ml) was heated for 2.5 hours while refluxing. To the reaction mixture was added a saturated aqueous solution of NaHCO3 and ether, and the resulting crystal was collected by filtration, to yield 2-imino-5-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]-4-thiazolidinone (0.86 g, 88%) (recrystallized from chloroform-methanol) as a colorless crystal.
Reaction SMILES: ClC1C=C(Cl)C=CC=1N1CCN=C1[CH:14]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)CCN1C=CN=C1.[N:28]1([CH2:33][CH2:34][OH:35])[CH:32]=[CH:31][N:30]=[CH:29]1.C(N(CC)CC)C.C1(C)C=CC([S:49](Cl)(=[O:51])=[O:50])=CC=1>ClCCl>[N:28]1([CH2:33][CH2:34][O:35][S:49]([C:27]2[C:22]([CH3:14])=[CH:23][CH:24]=[CH:25][CH:26]=2)(=[O:51])=[O:50])[CH:32]=[CH:31][N:30]=[CH:29]1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OCCn1ccnc1
Reactant: Clc1ccc(N2CCN=C2C(CCn2ccnc2)c2ccccc2)c(Cl)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccccc1S(=O)(=O)OCCn1ccnc1
Temperature: -10 °C

Procedure:
1-(2,4-Dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole To a stirred solution of 2-(imidazol-1-yl)ethanol (1.9 g, 0.0156 mol), triethylamine (2.8 ml, 0.0187 mol), and 4-N,N-dimethylaminopyridine (20 mg) in dichloromethane (20 ml) at a temperature of -78° C. under nitrogen atmosphere, was added p-toluenesulphonyl chloride (3.6 g, 0.0187 mol) in dichloromethane (10 ml). The reaction mixture was allowed to warm to -10° C. and was then quenched by the addition of saturated aqueous sodium hydrogen carbonate. The organic phase was separated and the aqueous phase extracted with dichloromethane. The organic phases were combined, washed with brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield colorless crystals of 2-(imidazol-1-yl)-1-toluenesulphonyloxyethane (4.23 g). n-Butyllithium (3.9 ml, 0.0059 mol, 1.5M in hexane) was added to a stirred solution of 1-(2,4-dichlorophenyl)-4,5-dihydro-2-phenylmethylimidazole (1.5 g, 0.0049 mol) in dry tetrahydrofuran (10 ml) at -78° C. under a nitrogen atmosphere. Copper(I)bromide-dimethyl sulphide complex (50 mg, 0.0024 mol) was added to the reaction mixture. After a period of one hour, a solution of 2-(imidazol-1-yl)-1-toluenesulphonyloxyethane (2 g, 0.0072 mol) in tetrahydrofuran (7 ml) was added to the reaction mixture. The resulting mixture was allowed to warm to room temperature and allowed to react for 15 hours before being quenched with saturated aqueous ammonium chloride. The phases were separated and the aqueous phase extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous magnesium sulphate and concentrated under reduced pressure to yield an oil which was chromatographed on silica gel with ammonia/methanol/ethyl acetate (1:4:45) to yield 1-(2,4-dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole (1 g) which upon treatment with ethereal hydrogen chloride yielded the hydrochloride salt of 1-(2,4-dichlorophenyl)-4,5-dihydro-2-[3-(imidazol-1-yl)-1-phenylpropyl]imidazole. (Found C, 49.00; H, 5.03; N, 10.76. C21H22N4Cl4.9/4H2O requires C, 49.19; H, 5.21; N, 10.93) having the formula ##STR43##
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].CC1(C)C(C)(C)OB([C:29]2[CH:33]=[CH:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:30]=2)O1>>[C:37]([O:36][C:34]([N:31]1[CH:32]=[CH:33][C:29]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:30]1)=[O:35])([CH3:40])([CH3:38])[CH3:39]
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Reactant: CC(C)(C)OC(=O)n1ccc(B2OC(C)(C)C(C)(C)O2)c1
Product: COC(=O)c1cc(C2CC2)c2c(C)c(-c3ccn(C(=O)OC(C)(C)C)c3)ccn2c1=O
Yield: 62 %

Procedure:
Methyl 8-(1-(tert-butoxycarbonyl)-1H-pyrrol-3-yl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A using methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.34 mmol) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1-carboxylate (151.0 mg, 0.51 mmol). Purification by flash silica column chromatography (CH2Cl2:MeOH) (1:0 to 94:6) afforded the title compound as a yellow solid (89 mg, 61%). ESI-MS m/z: 423 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:21][CH2:22][N:23]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][C:16]([O:18]CC)=[O:17])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.O.[OH-].[Li+].Cl>C1COCC1.O>[C:1]([O:5][C:6]([N:8]([CH2:21][CH2:22][N:23]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH:9]1[CH2:10][CH2:11][CH:12]([CH2:15][C:16]([OH:18])=[O:17])[CH2:13][CH2:14]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CCOC(=O)CC1CCC(N(CCN(C(=O)OC(C)(C)C)c2ccccn2)C(=O)OC(C)(C)C)CC1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)N(CCN(C(=O)OC(C)(C)C)C1CCC(CC(=O)O)CC1)c1ccccn1
Reaction time: 2.25 h

Procedure:
To a solution of ethyl 2-[4-[tert-butoxycarbonyl-[2-[tert-butoxycarbonyl(2-pyridyl)amino]ethyl]amino]cyclohexyl]acetate (968 mg, 1.91 mmol) in THF (3 mL); methanol (3 mL) and water (6 mL) was added lithium hydroxide monohydrate (397 mg, 9.7 mmol). The resulting solution was stirred for 2.25 hr, then acidified to pH 3 with 1N HCl. The resulting mixture was extracted with dichloromethane (4 times). The combined organic extract was dried over magnesium sulfate and concentrated. The residue was purified by silica chromatography (10 g silica; eluted with 40-100% ethyl acetate in hexanes) to give the title compound as a 6:1 mixture of trans:cis isomers.
Reaction SMILES: C([O:3][C:4](=[O:23])[C:5]1[CH:10]=[C:9]([C:11](=[O:17])[N:12]([CH3:16])[CH2:13][CH2:14][CH3:15])[CH:8]=[C:7]([C:18](=[O:22])[NH:19][CH2:20][CH3:21])[CH:6]=1)C.[OH-].[Li+].C1COCC1>O>[CH2:20]([NH:19][C:18]([C:7]1[CH:6]=[C:5]([CH:10]=[C:9]([C:11](=[O:17])[N:12]([CH3:16])[CH2:13][CH2:14][CH3:15])[CH:8]=1)[C:4]([OH:23])=[O:3])=[O:22])[CH3:21]
Reactant: CCCN(C)C(=O)c1cc(C(=O)NCC)cc(C(=O)OCC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCN(C)C(=O)c1cc(C(=O)O)cc(C(=O)NCC)c1
Yield: 72.5 %

Procedure:
Stir a solution of 3-ethylcarbamoyl-5-(methyl-propylcarbamoyl)-benzoic acid ethyl ester (157 mg, 0.5 mmol), 1 N aqueous lithium hydroxide (2.45 mL, 2.45 mmol) and THF (2.45 mL) at room temperature overnight. Dilute the reaction with water and extract with dichloromethane. Acidify the aqueous with 5 N HCl , extract the aqueous with dichloromethane and dry (magnesium sulfate) and concentrate to give the title compound (106 mg, 74%).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[CH:19]=[C:18]([NH:20][CH:21]([CH3:23])[CH3:22])[C:14]([C:15]([OH:17])=O)=[CH:13][N:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[NH2:24][C:25](=[N:31][NH2:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:24][C:25](=[N:31][NH:32][C:15](=[O:17])[C:14]1[C:18]([NH:20][CH:21]([CH3:23])[CH3:22])=[CH:19][C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]3[N:3]=[CH:2][S:1][C:5]=3[CH:6]=2)=[N:12][CH:13]=1)[C:26]([O:28][CH2:29][CH3:30])=[O:27]
Reactant: CC(C)Nc1cc(Nc2ccc3ncsc3c2)ncc1C(=O)O
Reactant: CCOC(=O)C(N)=NN
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)C(N)=NNC(=O)c1cnc(Nc2ccc3ncsc3c2)cc1NC(C)C
Reaction time: 4 h

Procedure:
To a stirred solution of 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinic acid (4) (500 mg, 3.8 mmol) and ethyl 2-amino-2-hydrazonoacetate (6) (3.8 mmol, 1 equiv.) in DMF (10 mL), HATU (7.63 mmol, 2 equiv.) and DIPEA (15.2 mmol, 4 equiv.) were added and stirred for 4 h. The reaction mixture was concentrated under reduced pressure to remove excess of DMF. The residue obtained was partitioned between water and EtOAc. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent to afford the title compound.
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]([Mg]Br)[CH3:11].B(F)(F)F.[OH-].[Na+]>C(OCC)C.C(OCC)(=O)C>[CH2:7]([C:8]1([NH2:9])[CH2:11][CH2:10]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#CCc1ccccc1
Reactant: CC[Mg]Br
Agent: FB(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: NC1(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.5 %

Procedure:
To a solution of phenylacetonitrile (3 g, 25.61 mmol) and tetraisopropylorthotitanate (8 ml, 27.15 mmol) in diethyl ether (Et2O)/tetrahydrofuran (THF) (1/1, 100 ml) ethyl-magnesiumbromide (49.33 mmol) was added at room temperature. The exothermic mixture was stirred for 1 h at room temperature. Then BF3×Et2O (49.34 mmol) was added and the mixture was stirred for 1 h. The mixture was poured into a cold aqueous solution of NaOH (10%) and diluted with ethyl acetate. The mixture was filtered, and the organic layer was washed with water and brine, dried over MgSO4, filtered, and the solvent evaporated under reduced pressure to give the product as a yellow oil (3.6 g, 96%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][C:5]2([CH3:13])[CH3:12].B([O-])[O-].Br[C:18]1[N:23]2[N:24]=[CH:25][N:26]=[C:22]2[C:21]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][N:37]([CH:40]([CH3:42])[CH3:41])[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)=[N:20][CH:19]=1>>[CH:40]([N:37]1[CH2:36][CH2:35][N:34]([C:31]2[CH:30]=[CH:29][C:28]([NH:27][C:21]3[C:22]4[N:23]([N:24]=[CH:25][N:26]=4)[C:18]([C:2]4[CH:3]=[C:4]5[C:8](=[CH:9][CH:10]=4)[C:7](=[O:11])[NH:6][C:5]5([CH3:13])[CH3:12])=[CH:19][N:20]=3)=[CH:33][CH:32]=2)[CH2:39][CH2:38]1)([CH3:42])[CH3:41]
Reactant: CC1(C)NC(=O)c2ccc(Br)cc21
Reactant: CC(C)N1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1
Agent: [O-]B[O-]
Product: CC(C)N1CCN(c2ccc(Nc3ncc(-c4ccc5c(c4)C(C)(C)NC5=O)n4ncnc34)cc2)CC1

Procedure:
5-Bromo-3,3-dimethyl-2,3-dihydroisoindol-1-one is converted to the corresponding boronate in a fashion analogous to Intermediate 6, Step 3. This is then used to prepare the title compound from (5-bromo[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-isopropylpiperazin-1-yl)-phenyl]amine using methods as described for Compound 120, Step 4. LCMS: Rt=0.92 (100%), m/z=497 (M+H)+.
Reaction SMILES: [CH3:1]I.[K].[CH3:4][S:5][C:6]1[C:11]([F:12])=[CH:10][NH:9][C:8](=[O:13])[N:7]=1>CN(C)C=O>[CH3:1][N:9]1[CH:10]=[C:11]([F:12])[C:6]([S:5][CH3:4])=[N:7][C:8]1=[O:13]
Reactant: CI
Reactant: CSc1nc(=O)[nH]cc1F
Agent: [K]
Solvent: CN(C)C=O
Product: CSc1nc(=O)n(C)cc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 76 %

Procedure:
Methyl iodide (0.017 mol) was added to the potassium salt of 4-methylthio-5-fluoropyrimid-2-one (0.012 mol) in dimethylformamide (50 ml) and the reaction mixture was stirred at room temperature for 24 h before evaporation at reduced pressure (1 mm Hg). The residue was extracted with chloroform and the solution was washed with aqueous 2 N NaOH, with water and was dried (MgSO4) before evaporation. The product was recrystallized from EtOAc/ligroin; yield 76%, m.p. 154° C. (Found: C, 41.48; H, 4.10. Calc. for C6H7FN2OS: C, 41.37; H, 4.05).