Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:47])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:45][CH3:46])=[C:12]([NH:15][C:16]3[N:29]4[C:20](=[N:21][C:22]5[C:27]([C:28]4=[O:30])=[C:26]([F:31])[CH:25]=[CH:24][CH:23]=5)[C:19]4[CH:32]=[CH:33][N:34]([S:35]([C:38]5[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=5)(=[O:37])=[O:36])[C:18]=4[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[CH3:48][CH:49]([NH2:51])[CH3:50]>C1COCC1.C(OCC)(=O)C>[CH3:47][N:2]([CH3:1])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:45][CH3:46])=[C:12]([NH:15][C:16]3[N:29]=[C:20]([NH:21][C:22]4[CH:23]=[CH:24][CH:25]=[C:26]([F:31])[C:27]=4[C:28]([NH:51][CH:49]([CH3:50])[CH3:48])=[O:30])[C:19]4[CH:32]=[CH:33][N:34]([S:35]([C:38]5[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=5)(=[O:37])=[O:36])[C:18]=4[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]
Reactant: CC(C)N
Reactant: COc1cc2c(cc1Nc1nc3c(ccn3S(=O)(=O)c3ccc(C)cc3)c3nc4cccc(F)c4c(=O)n13)N(C(=O)CN(C)C)CC2
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1cc2c(cc1Nc1nc(Nc3cccc(F)c3C(=O)NC(C)C)c3ccn(S(=O)(=O)c4ccc(C)cc4)c3n1)N(C(=O)CN(C)C)CC2
Temperature: 40 °C
Reaction time: 16 h

Procedure:
To a solution of 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (265 mg, 0.404 mmol) in THF (5 mL) was added (1-methylethyl)amine (0.694 mL, 8.08 mmol). The resulting mixture was let stir at 40° C. for 16 h at which time it was diluted with ethyl acetate and washed with a saturated ammonium chloride solution, a saturated sodium bicarbonate solution, water and a saturated brine solution. Organics were dried over sodium sulfate and solvents removed under reduced pressure. Residue was purified via SiO2 chromatography to afford 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-(1-methylethyl)benzamide. (210 mg, 0.294 mmol) as a yellow solid. (ESIMS (M+H)+=715)
Reaction SMILES: [C:1]([C:4]1[NH:8][N:7]=[C:6]([C:9]([NH:11][C@@H:12]([CH3:30])[CH2:13][N:14]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([N+]([O-])=O)[CH:20]=3)=[N:15]2)=[O:10])[CH:5]=1)(=[O:3])[CH3:2].[CH3:31][O-:32].C([N+](CCCC)(CCCC)CCCC)CCC>CO>[C:1]([C:4]1[NH:8][N:7]=[C:6]([C:9]([NH:11][C@@H:12]([CH3:30])[CH2:13][N:14]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([O:32][CH3:31])[CH:20]=3)=[N:15]2)=[O:10])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: C[O-]
Reactant: CC(=O)c1cc(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c([N+](=O)[O-])c3)n2)n[nH]1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CO
Product: COc1cc(-c2ccn(C[C@H](C)NC(=O)c3cc(C(C)=O)[nH]n3)n2)ccc1C#N
Reaction time: 144 h
Yield: 5 %

Procedure:
(S)-5-acetyl-N-(1-(3-(4-cyano-3-nitrophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamide (0.27 g, 0.663 mmol) was added to a flask and flushed with nitrogen. Dry THF was added and tetrabutylammonium methoxide solution in methanol (1.219 ml, 0.729 mmol) was added dropwise through a septum. During the reaction 1.754 ml of tetrabutylammonium methoxide solution in methanol was added and after reacting for 6 days the reaction was stopped. The crude product was evaporated and dissolved in DCM. The mixture was washed with water, dried and evaporated. Evaporation residue was dissolved in 20% methanol/DCM-solvent and filtered through silica wetted with the same solvent. The product was triturated using a small amount of DCM. Yield 5.00%. 1H-NMR (400 MHz; DMSO-d6): δ 1.16 (d, 3H), 2.5 (s, 3H), 3.94 (s, 3H), 4.31 (s, 2H), 4.40-4.50 (m, 1H), 6.88 (d, 1H), 7.31 (s, 1H), 7.46-7.54 (m, 2H), 7.71 (d, 1H), 7.80 (d, 1H), 8.49 (s, 1H), 14.12 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11]Cl)[N:10]=2)[CH:7]=1.Cl.Cl.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.C(N(CC)CC)C>C(O)CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11][N:25]3[CH2:24][CH2:23][N:22]([C:19]4[CH:18]=[CH:17][C:16]([Cl:15])=[CH:21][CH:20]=4)[CH2:27][CH2:26]3)[N:10]=2)[CH:7]=1
Reactant: Clc1ccc(N2CCNCC2)cc1
Reactant: ClCc1cn2cc(Cl)ccc2n1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: OCCO
Product: Clc1ccc(N2CCN(Cc3cn4cc(Cl)ccc4n3)CC2)cc1
Yield: 57.1 %

Procedure:
Following the general procedure of Example 11 and making noncritical variations, 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (Example 4, Step 1; 0.354 g), 1-(4-chlorophenyl)piperazine dihydrochloride (Aldrich; 0.475 g), triethylamine (0.552 g), and ethylene glycol (2 mL) give 0.363 g of the title compound after chromatography (silica gel, methanol/dichloromethane, 4/96) and crystallization from dichloromethane/hexane; mp 145-146° C.; MS m/z 360; IR (mineral oil) 823, 1500, 1496, 1225, 814 cm-1. 1H NMR (CDCl3) δ2.72, 3.19, 3.76, 6.83, 7.13, 7.19, 7.52, 7.53, 8.14.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]1[CH:14]1[C:23](=O)[C:22]2[C:21]([C:25]([O:27]C)=O)=[CH:20][CH:19]=[CH:18][C:17]=2[NH:16][CH:15]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[NH2:36][NH2:37]>>[CH2:1]([N:8]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]1[CH:14]1[C:23]2=[N:36][NH:37][C:25](=[O:27])[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([C:22]=32)[NH:16][CH:15]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1cccc2c1C(=O)C(c1nc(C)cn1Cc1ccccc1)C(c1ccccc1)N2
Reactant: NN
Solvent: O
Product: Cc1cn(Cc2ccccc2)c(C2c3n[nH]c(=O)c4cccc(c34)NC2c2ccccc2)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 16 %

Procedure:
A mixture of methyl 3-(1-benzyl-4-methyl-1H-imidazol-2-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (250 mg, 0.57 mmol) and hydrazine monohydrate (3 mL) was stirred room temperature for 5 h. The resulting mixture was evaporated under reduced pressure to 15 ml and then filtered; the filtrate was concentrated to give 9-(1-benzyl-4-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one as a white solid (40 mg, yield 16%). LC-MS (ESI) m/z: 434 (M+1)+.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[N:6]=[C:5]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:4]=1.[O:17]1CCOCC1>[OH-].[Na+].O>[OH:17][CH2:2][C:3]1[CH:8]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[N:6]=[C:5]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:4]=1
Reactant: C1COCCO1
Reactant: CC(C)(C)c1cc(CBr)cc(C(C)(C)C)n1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)(C)c1cc(CO)cc(C(C)(C)C)n1
Temperature: 25 °C

Procedure:
A heterogeneous solution of 4-bromomethyl-2,6-di-t-butylpyridine (Compound A, 1.743 g, 82% purity) in 20 ml of 12% NaOH in water and 10 ml of 1,4-dioxane was refluxed for 12 hours. The solution spontaneously separated into two layers as it cooled to room temperature. The upper layer was separated and ethyl acetate was added. This organic layer was then washed with brine, water and dried over MgSO4. The desired product was purified by column chromatography (ethyl acetate/hexane 1/9) to give a white solid. 1H NMR δ7.09 (s, 2H), 4.67 (d, J=4.4 Hz, 2H), 2.3 (b, 1H), 1.36 (s, 18H).
Reaction SMILES: [C:1]1([NH:7][NH:8][C:9](=[O:21])[C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([S:17](=[O:20])(=[O:19])[NH2:18])[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)P(=O)(N(C)C)N(C)C.C(=O)(O)[O-].[Na+].[CH2:38](Br)[CH:39]=[CH2:40]>C(OCC)(=O)C>[CH2:40]([N:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[NH:8][C:9](=[O:21])[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([S:17](=[O:20])(=[O:19])[NH2:18])[CH:11]=1)[CH:39]=[CH2:38]
Reactant: NS(=O)(=O)c1cc(C(=O)NNc2ccccc2)ccc1Cl
Reactant: C=CCBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: C=CCN(NC(=O)c1ccc(Cl)c(S(N)(=O)=O)c1)c1ccccc1
Temperature: 25 °C

Procedure:
In a three necked 1 liter round bottom reaction vessel equipped with a mechanical stirrer and reflux condenser were placed 48.8 g (0.15 mol) of the compound of Example 8 and 125 ml of hexamethylphosphorictriamide. The mixture was heated with stirring under nitrogen to 80°-85° C. To this solution 126 g (1.5 mol) of sodium bicarbonate powder was added portionwise followed by 20 g (0.17 mol) of allyl bromide. After 2.25 hours an additional 1.8 g (0.015 mol) of allyl bromide was added. After 29 hours of heating the reaction mixture was cooled to room temperature diluted with 700 ml of ethyl acetate, and the slurry was cross washed with water and diluted brine. The ethyl acetate was separated, dried with magnesium sulfate, clarified and taken to dryness under vacuum. The crude reaction mixture was crystallized from chloroform yielding 26.2 g of analytically pure product mp 99°-101° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=O.[CH3:12][C:13]([S@@:16]([NH2:18])=[O:17])([CH3:15])[CH3:14].O>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])/[CH:5]=[N:18]/[S@:16]([C:13]([CH3:15])([CH3:14])[CH3:12])=[O:17]
Reactant: COc1ccc(C=O)cc1F
Reactant: CC(C)(C)[S@@](N)=O
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(/C=N/[S@@](=O)C(C)(C)C)cc1F
Temperature: 65 °C
Yield: 89.7 %

Procedure:
To a solution of 3-fluoro-4-methoxybenzaldehyde (2.0 g, 13 mmol) in THF (40 mL) was added (S)-2-methylpropane-2-sulfinamide (2.84 g, 23.4 mmol) and Ti(OEt)4 (5.92 g, 26.0 mmol). The reaction mixture was heated at 65° C. for 12 h. After cooling to RT, the mixture was poured into water. The solid was filtered, and the filtrate was extracted with EtOAc (3×100 mL). The filtrate was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with EtOAc/petroleum ether (1:4) to afford 3.0 g (90%) of (S,E)-N-(3-fluoro-4-methoxybenzylidene)-2-methylpropane-2-sulfinamide (66). LCMS (ESI) m/z: 258.1 [M+H]+.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)[C:5]([F:18])=[CH:4][N:3]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][CH3:29])[NH2:24]>>[CH3:19][O:20][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=3)[C:5]([F:18])=[CH:4][N:3]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]
Reactant: COc1ccc(N)cc1OC
Reactant: CCOc1ccc(Nc2nc(Cl)ncc2F)cc1
Product: CCOc1ccc(Nc2nc(Nc3ccc(OC)c(OC)c3)ncc2F)cc1

Procedure:
In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of 2-chloro-N4-(4-ethoxyphenyl)-5-fluoro-4-pyrimidineamine with 3,4-dimethoxyaniline gave N2-(3,4-dimethoxyphenyl)-N4-(4-ethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine. 1H NMR (CDCl3): δ 7.89 (d, 1H, J=3 Hz), 7.45 (bd, 2H, J=9 Hz), 7.20 (d, 1H, J=2.4 Hz), 6.96-6.77 (m, 5H), 6.63 (bs, 1H), 4.03 (q, 2H, J=7.2 Hz), 3.86 (s, 3H), 3.72 (s, 3H), 1.42 (t, 3H, J=7.2 Hz); 19F NMR (CDCl3): −47473.
Reaction SMILES: [CH2:1]1[CH:6]([CH2:7][CH:8]2[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]2)[CH2:5][CH2:4][CH:3]([NH2:15])[CH2:2]1.[C:16](=[O:27])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])N.N>>[CH2:19]([O:18][C:16]([NH:15][CH:3]1[CH2:2][CH2:1][CH:6]([CH2:7][CH:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:27])[CH2:10][CH2:9]2)[CH2:5][CH2:4]1)=[O:27])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: CCCCCCCCOC(N)=O
Reactant: NC1CCC(CC2CCC(N)CC2)CC1
Agent: N
Product: CCCCCCCCOC(=O)NC1CCC(CC2CCC(NC(=O)OCCCCCCCC)CC2)CC1
Temperature: 100 °C

Procedure:
Agitated in a reaction vessel are 210 parts of 4,4'-diaminodicyclohexylmethane with 360 parts of O-octyl carbamate and 150 parts of n-octanol-(1) at a reflux temperature of 185° C.-205° C. for 2 hours while the ammonia is removed by means of distillation. At this point, an additional 650 parts of n-octanol are allowed to flow into the reaction mixture and the reaction is continued at reflux temperature for 10 hours. The reaction mixture, which has been cooled to 100° C., is filtered, and the product is allowed to crystallize by cooling the filtrate. By filtration, washing with octanol and drying, 468 parts of bis(4-octoxycarbonylaminocyclohexyl)methane, C31H58N2O4 (molecular weight 522) are obtained corresponding with 89.6 percent theory relative to 4,4'-bisaminodicyclohexylmethane. The melting point is 129° C.-130° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][C:18](OCC)=[O:19])[CH:13]=[N:14]2)=[N:9][CH:8]=1.[NH3:27].CO>>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][C:18]([NH2:27])=[O:19])[CH:13]=[N:14]2)=[N:9][CH:8]=1
Reactant: N
Reactant: CCOC(=O)Cc1cnc2cc(OCc3ccc(F)c(F)c3)cnc2c1
Solvent: CO
Product: NC(=O)Cc1cnc2cc(OCc3ccc(F)c(F)c3)cnc2c1
Temperature: 25 °C
Reaction time: 30 h

Procedure:
Ethyl 2-(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetate (1.95 g, 5.44 mmol) was treated with a solution of ammonia in MeOH (7 M, 30 mL, 245 mmol). The slurry was stirred at ambient temperature for 30 h. The resulting precipitate was filtered and washed with MeOH to give the title compound as a cream colored solid. The crude product was azeotrope dried with toluene to remove traces of ammonia then dried on high vacuum for 48 h to give the title compound (1.79 g, 82%) as a pure white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.81 (t, J=2.0 Hz, 2H), 8.21 (d, J=1.4 Hz, 1H), 7.88 (d, J=2.6 Hz, 1H), 7.75-7.58 (m, 2H), 7.50 (td, J=8.4, 10.7 Hz, 1H), 7.45-7.36 (m, 1H), 7.05 (br s, 1H), 5.34 (s, 2H), 3.66 (s, 2H). [M+H]=330.2.
Reaction SMILES: [CH:1]1([C:5]2[C:6]([O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:21][S:22]([CH2:25][C:26]([NH2:34])([CH3:33])[C:27]1[N:31]=[C:30]([CH3:32])[O:29][N:28]=1)(=[O:24])=[O:23]>>[CH3:21][S:22]([CH2:25][C:26]([NH:34][C:11]([C:8]1[CH:7]=[C:6]([O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])[C:5]([CH:1]2[CH2:2][CH2:3][CH2:4]2)=[CH:10][N:9]=1)=[O:13])([CH3:33])[C:27]1[N:31]=[C:30]([CH3:32])[O:29][N:28]=1)(=[O:23])=[O:24]
Reactant: C[C@H](Oc1cc(C(=O)O)ncc1C1CCC1)C(F)(F)F
Reactant: Cc1nc(C(C)(N)CS(C)(=O)=O)no1
Product: Cc1nc(C(C)(CS(C)(=O)=O)NC(=O)c2cc(O[C@@H](C)C(F)(F)F)c(C3CCC3)cn2)no1

Procedure:
The title compound was synthesized in analogy to Example 23b, using 5-Cyclobutyl-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (Example 110e) and 2-Methanesulfonyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethylamine (Example 109d) as starting materials and isolated (77 mg, 57%) as a white solid; MS (ESI, m/z): 491.6 (M+H+).
Reaction SMILES: C(N(CC)C(C1C=CC=CC=1[S:12]([C:15]1[C@H:16]([CH3:46])[C@@H:17]2[C@@H:34]([C@H:35]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH3:36])[C:33](=[O:45])[N:18]2[C:19]=1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1)=[O:21])(=O)=O)=O)C.[CH3:49][N:50]([CH3:72])[C:51]([C@@H:53]1[CH2:57][C@H:56](S)[CH2:55][N:54]1[C:59]([O:61][CH2:62][C:63]1[CH:68]=[CH:67][C:66]([N+:69]([O-:71])=[O:70])=[CH:65][CH:64]=1)=[O:60])=[O:52]>>[CH3:49][N:50]([CH3:72])[C:51]([C@@H:53]1[CH2:57][C@H:56]([S:12][C:15]2[C@H:16]([CH3:46])[C@@H:17]3[C@@H:34]([C@H:35]([O:37][Si:38]([C:41]([CH3:42])([CH3:43])[CH3:44])([CH3:39])[CH3:40])[CH3:36])[C:33](=[O:45])[N:18]3[C:19]=2[C:20]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=2)=[O:21])[CH2:55][N:54]1[C:59]([O:61][CH2:62][C:63]1[CH:64]=[CH:65][C:66]([N+:69]([O-:71])=[O:70])=[CH:67][CH:68]=1)=[O:60])=[O:52]
Reactant: CCN(CC)C(=O)c1ccccc1S(=O)(=O)C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]2[C@H]1C
Reactant: CN(C)C(=O)[C@@H]1C[C@H](S)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N(C)C)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Yield: 78 %

Procedure:
Following a procedure similar to that described in Example 18, but using 76 mg of 4-nitrobenzyl (1R, 5S,6S)-2-(2-diethylcarbamoylphenylsulfonyl)-1-methyl-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-carbapen-2-em-3-carboxylate (prepared as described it Example 42) and 46 mg of (2S,4S)-dimethylcarbamoyl-1-(4-nitrobenzyloxycarbonyl)-4-mercaptopyrrolidine, the title compound was obtained in a yield of 78%.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([OH:13])=[O:12])[NH:6]2.[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O)[CH3:15]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([OH:13])=[O:12])[NH:6]2)[CH3:15]
Reactant: O=C(O)c1cc2c(Br)cccc2[nH]1
Reactant: CCc1ccccc1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCc1ccccc1-c1cccc2[nH]c(C(=O)O)cc12

Procedure:
To a mixture of 0.28 g of 4-bromo-indole-2-carboxylic acid and 0.069 g of tetrakistriphenylphosphinepalladium in 11 ml of toluene and 2 ml of 2M soda is added a solution of 0.300 g of 2-ethylphenylboronic acid in 3 ml of ethanol. This mixture is refluxed for 16 h, filtered and the aqueous phase acidified with 2N HCl and extracted with ethyl acetate. Concentration of the organic phase gives the product as a brownish powder, m.p. 230-233°, sufficiently pure for the next step.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C1COCC1>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH2:16][N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCN(C(=O)c2ccc(C=O)cc2)CC1
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)N1CCN(C(=O)c2ccc(CN3CCOCC3)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-(4-isopropyl-piperazine-1-carbonyl)-benzaldehyde (4.0 g, 15.38 mmol) in THF (40 mL) was added morpholine (2.9 g, 33.83 mmol), and the resulting mixture was stirred at room temperature for 1 h before it was cooled to 0° C. with an ice bath. The reaction mixture was then treated with NaBH(OAc)3 (4.56 g, 21.53 mmol) in portions over 15 min. The resulting suspension was stirred at room temperature until it was deemed complete by HPLC. After completion, 10% NaOH (25 mL) was added and the reaction was vigorously agitated for 15 min. The phases were separated and the aqueous layer was extracted with THF (20 mL). The organic layers were combined, dried (MgSO4), filtered and concentrated to yield the title compound as a yellow oil.
Reaction SMILES: [NH2:1][C:2]([N:4]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)[CH2:5][CH2:6][C:7]1[CH:21]=[CH:20][C:10]([O:11][C:12]([CH3:19])([CH3:18])[C:13]([O:15]CC)=[O:14])=[CH:9][CH:8]=1)=[S:3].[Cl:33][C:34]1[CH:43]=[CH:42][C:37]([C:38](=O)[CH2:39]Br)=[CH:36][CH:35]=1>>[Cl:33][C:34]1[CH:43]=[CH:42][C:37]([C:38]2[N:1]=[C:2]([N:4]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[CH2:5][CH2:6][C:7]3[CH:8]=[CH:9][C:10]([O:11][C:12]([CH3:19])([CH3:18])[C:13]([OH:15])=[O:14])=[CH:20][CH:21]=3)[S:3][CH:39]=2)=[CH:36][CH:35]=1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CCN(Cc2ccc(C(F)(F)F)cc2)C(N)=S)cc1
Reactant: O=C(CBr)c1ccc(Cl)cc1
Product: CC(C)(Oc1ccc(CCN(Cc2ccc(C(F)(F)F)cc2)c2nc(-c3ccc(Cl)cc3)cs2)cc1)C(=O)O

Procedure:
Similarly prepared from ethyl 2-[4-(2-{(aminocarbonothioyl)[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate and 4-chlorophenacyl bromide.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH2:20]([NH2:26])[C:21]1[O:25][CH:24]=[CH:23][CH:22]=1>>[O:25]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH2:20][NH:26][C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccco1
Reactant: O=C(Nc1nc2cccc(Cl)n2n1)c1ccccc1
Product: O=C(Nc1nc2cccc(NCc3ccco3)n2n1)c1ccccc1

Procedure:
The title compound was prepared following procedure described for example 30 but starting from N-(5-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl)benzamide ((B3), 50 mg; 0.18 mmol; 1.0 eq.) and furfurylamine (1.0 mL) as a beige powder (31 mg, 51%). HPLC, Rt: 2.20 min. (purity 94.1%). LC/MS, M+(ESI): 334.1, M−(ESI): 332.1.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.S(=O)(=O)(O)[OH:12].[OH-].[K+].Cl>O>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:12])[CH:9]=2)[NH:4][N:3]=1
Reactant: Nc1n[nH]c2ccccc12
Reactant: O=S(=O)(O)O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Nc1n[nH]c2ccc(O)cc12
Temperature: 80 °C
Reaction time: 3 h
Yield: 51.1 %

Procedure:
A mixture consisting of 5 g of 3-aminoindazole and 4.3 g of 95% sulfuric acid was stirred for 3 hours at 80° C. To the mixture was added 13 ml of water, and the pH of the mixture was adjusted to 14 with potassium hydroxide. The mixture was washed twice with 20 ml of chloroform, and water was removed under reduced pressure. The residue thus obtained was added with 12.5 g of potassium hydroxide and 0.6 ml of water, and the mixture was stirred for 8 hours at 250° C. After cooling, to the mixture was added hydrochloric acid to separate crystals. The crystals were obtained by filtration and dried to give 2.86 g of 3-amino-5-hydroxyindazole having the following analytical values.
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12](O)[C:13]1[O:17][CH:16]=[CH:15][CH:14]=1)([O:3][CH2:4][CH3:5])=[O:2].C(O)=[O:20].C([O-])=O.[Na+].C1(C=CC(O)=CC=1)O>O1CCOCC1.O>[C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH:13]([OH:17])[CH:14]=[CH:15][C:16]1=[O:20])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)CCCCCCC(O)c1ccco1
Reactant: O=CO
Agent: O=C[O-]
Agent: Oc1ccc(O)cc1
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCOC(=O)CCCCCCC1C(=O)C=CC1O

Procedure:
A stirred mixture of 2.0g (7.87 mmol) of α-(6-carbethoxyhexyl)furfuryl alcohol (Example 4), 5.93 ml of 97% formic acid, 268 mg of sodium formate, 10 mg of hydroquinone, and 40 ml of 3:2 dioxane-water is stirred at reflux for 18 hr. The solution is cooled, saturated with salt, and extracted with ether. The extract is washed with brine, dried over magnesium sulfate, and concentrated to give an amber oil.