Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[CH:6][N:7]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[C:44]1([CH2:50][C:51]([NH:53][NH2:54])=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C>[C:44]1([CH2:50][C:51]([NH:53][NH:54][C:11]([C:9]2[NH:8][C:5]3=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:13])=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: O=C(O)c1cc2cc(Cl)ncc2[nH]1
Reactant: NNC(=O)Cc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Cc1ccccc1)NNC(=O)c1cc2cc(Cl)ncc2[nH]1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 8, 50 mg, 0.25 mmol) in DMF (10 mL) was added DIPEA (89 μL, 0.51 mmol), HOBt (34 mg, 0.25 mmol), EDCI (63 mg, 0.33 mmol) and phenylacetic acid hydrazide (38 mg, 0.25 mmol) and the mixture was stirred at rt for 72 h. The reaction mixture was partitioned between water (50 mL) and ethyl acetate (3×30 mL). The combined organics were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed on silica gel eluting with methanol/dichloromethane (1:19) to give the title compound. m/z (ES+)=329 [M+H]+; RT=3.07 min.
Reaction SMILES: S1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]2[C:14]([C:15]3[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=3)[CH2:18][NH:19][C:20]([C:22]3[C:23](=[O:37])[N:24]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=4)[CH:25]=[CH:26][CH:27]=3)=[O:21])=[CH:13][NH:12][C:9]2=[N:10][CH:11]=1.BrC1[O:43]C=CC=1.[Br-]>[Pd]>[O:43]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]2[C:14]([C:15]3[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=3)[CH2:18][NH:19][C:20]([C:22]3[C:23](=[O:37])[N:24]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=4)[CH:25]=[CH:26][CH:27]=3)=[O:21])=[CH:13][NH:12][C:9]2=[N:10][CH:11]=1
Reactant: Brc1ccco1
Reactant: O=C(NCc1cccc(-c2c[nH]c3ncc(-c4cccs4)cc23)c1)c1cccn(Cc2ccc(F)c(F)c2)c1=O
Agent: [Pd]
Agent: [Br-]
Product: O=C(NCc1cccc(-c2c[nH]c3ncc(-c4ccco4)cc23)c1)c1cccn(Cc2ccc(F)c(F)c2)c1=O

Procedure:
Except where indicated, 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid 3-(5-furan-2-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-benzylamide was synthesized as per Example 95, 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid 3-(5-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-benzylamide using 2-Bromo-furan as bromide in the second palladium coupling, to yield the product. 1H NMR (400 MHz, CDCl3-MeOH-d4) ppm 10.237 (m, 1H) 8.813 (s, 1H) 8.594 (s, 1H) 8.510 (d, J=7.0 Hz, 1H) 7.669 (s, 1H) 7.587 (s, 1H) 7.543 (d, J=6.1 Hz, 1H) 7.508 (s, 1H) 7.490-7.391 (m, 2H) 7.346 (d, J=6.7 Hz, 1H) 7.132-7.014 (m, 2H) 6.991-6.925 (m, 1H) 6.868 (d, J=2.9 Hz, 1H) 6.495 (m, 1H) 6.440 (t, J=6.7 Hz, 1H) 5.079 (s, 2H) 4.677 (m, 2H); MS m/z=537.31 M+H.
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([N:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([O:27]CC)=[O:26])=[CH:21][CH:20]=3)=[CH:15][C:14]=2[C:30]2[NH:34][N:33]=[N:32][N:31]=2)[C:10]([NH2:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].Cl>C(O)C>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[C:5]([N:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([OH:27])=[O:26])=[CH:23][CH:24]=3)=[CH:15][C:14]=2[C:30]2[NH:34][N:33]=[N:32][N:31]=2)[C:10]([NH2:12])=[O:11])[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(N(C(N)=O)c3cccc(C(F)(F)F)c3)c(-c3nnn[nH]3)c2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: NC(=O)N(c1cccc(C(F)(F)F)c1)c1ccc(-c2ccc(C(=O)O)cc2)cc1-c1nnn[nH]1
Temperature: 25 °C
Yield: 90.1 %

Procedure:
To a suspension of 3-trifluoromethylphenyl-4-(4-ethoxycarbonylphenyl)-2-(5-tetrazolyl)phenyl urea (4.5 g, 9 mmol) in 96% ethanol was added sodium hydroxide (4 N, 25 mL). The reaction was heated to reflux for 30 min, then cooled to room temperature and acidified with hydrochloric acid. The precipitate was filtered off to give 3.8 g of the desired material. M.p. 300° C. (dec.).
Reaction SMILES: [CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([N:12]=[CH:13][C:14]=2[C:15](O)=[O:16])[CH:11]=1)(=[O:5])=[O:4].C(Cl)(=O)C([Cl:22])=O>C(Cl)(Cl)Cl>[CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([N:12]=[CH:13][C:14]=2[C:15]([Cl:22])=[O:16])[CH:11]=1)(=[O:5])=[O:4]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CN(C)S(=O)(=O)c1ccc2c(C(=O)O)cnn2c1
Solvent: ClC(Cl)Cl
Product: CN(C)S(=O)(=O)c1ccc2c(C(=O)Cl)cnn2c1

Procedure:
6-Dimethylsulfamoyl-pyrazolo[1,5-a]pyridine-3-carboxylic acid (200 mg, 0.57 mmol) are dissolved in 4 ml chloroform and oxalylchloride (97 μl, 1.14 mmol; Fluka) are added. The reaction is refluxed for 3 hours and then volatiles are removed under reduced pressure. The crude product is directly used in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]#[N:29])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]([CH:14]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]([O:17]CC)=[O:16])[C:10](=[O:27])[CH:9]=2)[CH:7]=1.[OH-].[Li+]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]#[N:29])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]([CH:14]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]([OH:17])=[O:16])[C:10](=[O:27])[CH:9]=2)[CH:7]=1
Reactant: CCOC(=O)C(Cc1ccccc1)n1ccc(-c2cc(Cl)ccc2C#N)cc1=O
Agent: [Li+]
Agent: [OH-]
Product: N#Cc1ccc(Cl)cc1-c1ccn(C(Cc2ccccc2)C(=O)O)c(=O)c1

Procedure:
300 mg (purity 94%, 0.69 mmol) of ethyl 2-[4-(5-chloro-2-cyanophenyl)-2-oxopyridin-1(2H)-yl]-3-phenylpropanoate (racemate) were hydrolysed with lithium hydroxide according to General Method 6B. Yield: 129 mg (purity 89%, 43% of theory)
Reaction SMILES: [CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC([N:30]1[CH2:35][CH2:34][CH2:33][C:32]([C:37]#[CH:38])([OH:36])[CH2:31]1)=O)(C)(C)C.C(N(CC)CC)C.[Cl-].N>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.[Cu]I.C(OCC)(=O)C.O.CN(C)C=O.CO>[CH2:1]([C:8]1[C:13]([C:38]#[C:37][C:32]2([OH:36])[CH2:33][CH2:34][CH2:35][NH:30][CH2:31]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#CC1(O)CCCN(C(=O)OC(C)(C)C)C1
Reactant: CO[C@@H]1CN(c2ccc(I)c(Cc3ccccc3)n2)C[C@H]1O
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CO[C@@H]1CN(c2ccc(C#CC3(O)CCCNC3)c(Cc3ccccc3)n2)C[C@H]1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.6 %

Procedure:
A mixture of 450 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1yl]-pyridine (Production Example 1), 272 mg of 1-tert-butoxycarbonyl-3-ethynyl-3-piperidinol (Production Example 15), 63.6 mg of tetrakis(triphenylphosphine)palladium (0), 41.9 mg of copper (I) iodide, 460 μl of triethylamine, 5 ml of methanol and 1 ml of N,N-dimethyl formamide was heated under reflux under nitrogen atmosphere for 3 hours. After standing to cool, water, ethyl acetate, an aqueous ammonia chloride solution were added to the reaction mixture, and the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then the solvent was removed. To the residue were added 2 ml of trifluoroacetic acid and 2 ml of dichloromethane, followed by stirring at room temperature for 1 hour. The reaction mixture was neutralized with an aqueous sodium hydrogen carbonate solution and an organic layer was separated by adding ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 387 mg of the entitled compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:13])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](F)(=[O:24])=[O:23])=[CH:18][C:17]=1N>>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([S:22]([O:13][C:5]2[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)(=[O:24])=[O:23])=[CH:20][CH:21]=1
Reactant: COc1ccc(S(=O)(=O)F)cc1N
Reactant: COc1cc(O)cc(OC)c1OC
Product: COc1ccc(S(=O)(=O)Oc2cc(OC)c(OC)c(OC)c2)cc1

Procedure:
3,4,5-trimethoxyphenol (504 mg) was processed as described in Example 43 (substituting 4-methoxybenzenesulfonyl chloride for 4-methoxymetanilyl fluoride) to provide 500 mg of the desired product.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH3:21])([CH3:20])[CH2:5][CH2:6][CH2:7][CH:8]([CH3:19])[CH2:9]/[CH:10]=[CH:11]/[C:12]([CH3:18])=[CH:13][C:14]([O:16]C)=[O:15])[CH3:2].CO.[OH-].[K+]>O>[CH2:1]([O:3][C:4]([CH3:20])([CH3:21])[CH2:5][CH2:6][CH2:7][CH:8]([CH3:19])[CH2:9]/[CH:10]=[CH:11]/[C:12]([CH3:18])=[CH:13][C:14]([OH:16])=[O:15])[CH3:2]
Reactant: CCOC(C)(C)CCCC(C)C/C=C/C(C)=CC(=O)OC
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCOC(C)(C)CCCC(C)C/C=C/C(C)=CC(=O)O

Procedure:
A mixture of 1 g. of trans methyl 11-ethoxy-3,7,11-trimethyldodeca-2,4-dienoate, 60 ml. of methanol, 0.5 g. of potassium hydroxide and 6 ml. of water is heated at reflux for about 8 hours. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed with water, dried over sodium sulfate and evaporated to yield trans 11-ethoxy-3,7,11-trimethyldodeca-2,4-dienoic acid.
Reaction SMILES: [CH3:1][C@@H:2]([CH2:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:4]I.C[O-].[Na+].[F:15][C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=2)[CH:19]=[CH:18][C:17]=1[C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1>CO>[F:15][C:16]1[CH:21]=[C:20]([C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:4][CH2:3][CH:2]([CH3:1])[CH2:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])=[CH:26][CH:27]=2)[CH:19]=[CH:18][C:17]=1[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:4][CH2:3][CH:2]([CH3:1])[CH2:6][CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])=[CH:31][CH:30]=1
Reactant: Oc1ccc(-c2ccc(-c3ccc(O)cc3)c(F)c2)cc1
Reactant: CC(C)CCC[C@H](C)CCI
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CC(C)CCCC(C)CCOc1ccc(-c2ccc(-c3ccc(OCCC(C)CCCC(C)C)cc3)c(F)c2)cc1
Reaction time: 5 h

Procedure:
80.5 g (0.3 mol) of (S)-3,7-dimethyl-1-iodoctane are added dropwise to a solution of 16.2 g (0.3 mol) of sodium methylate and 24.8 g (0.1 mol) of 1-fluoro-2,5-di(4-hydroxyphenyl)-benzene in 150 ml of methanol at the boiling point. After 5 hours, the mixture is worked up in the customary manner. Recrystallization gives pure 1-fluoro-2,5-di-[4-(3,7-dimethyloctyloxy)-phenyl]-benzene.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][C:15]=1[CH3:16].O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.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.CO>[CH3:9][C:10]1[CH:11]=[C:12]([C:2]2[CH:3]=[N:4][C:5]([NH2:8])=[N:6][CH:7]=2)[CH:13]=[CH:14][C:15]=1[CH3:16]
Reactant: Cc1ccc(B(O)O)cc1C
Reactant: Nc1ncc(Br)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: C1COCCO1
Product: Cc1ccc(-c2cnc(N)nc2)cc1C
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 250-mL 3-necked round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 5-bromopyrimidin-2-amine (5 g, 28.74 mmol, 1.00 equiv), 3,4-dimethylphenylboronic acid (4.4 g, 29.33 mmol, 1.00 equiv), dioxane (85 mL), methanol (29 mL), sodium carbonate (6.1 g, 57.55 mmol, 2.00 equiv) in water (29 mL), and Pd(PPh3)4 (664 mg, 0.57 mmol, 0.02 equiv). The resulting solution was stirred overnight at 100° C. in an oil bath. The mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with dichloromethane:methanol (50:1). This resulted in 6 g (crude) of 5-(3,4-dimethylphenyl)pyrimidin-2-amine as a yellow solid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[C:15]([NH2:17])=[O:16])[C:5]([Cl:18])=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:32]=[CH:31][C:23]2[N:24]([CH3:30])[C:25](=[O:29])[CH2:26][CH2:27][CH2:28][C:22]=2[CH:21]=1.Cl>CC(O)C.O1CCOCC1>[Cl:18][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[C:15]([NH2:17])=[O:16])=[N:7][C:2]([NH:19][C:20]2[CH:32]=[CH:31][C:23]3[N:24]([CH3:30])[C:25](=[O:29])[CH2:26][CH2:27][CH2:28][C:22]=3[CH:21]=2)=[N:3][CH:4]=1
Reactant: CN1C(=O)CCCc2cc(N)ccc21
Reactant: NC(=O)[C@@H]1CCCC[C@H]1Nc1nc(Cl)ncc1Cl
Agent: Cl
Solvent: C1COCCO1
Solvent: CC(C)O
Product: CN1C(=O)CCCc2cc(Nc3ncc(Cl)c(N[C@@H]4CCCC[C@H]4C(N)=O)n3)ccc21
Yield: 82.2 %

Procedure:
2-(2,5-Dichloro-pyrimidin-4-ylamino)-trans-cyclohexanecarboxylic acid amide (50.1 mg, 0.173 mmol) and 7-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (35.9 mg, 0.190 mmol) were slurried in iPrOH (2.0 mL) prior to adding ˜0.2 mL of 4N HCl in dioxane. This mixture was heated in a microwave reactor (sealed vessel) at 120° C. for 50 min. After quenching with saturated aqueous NaHCO3 solution (2 mL), the resulting precipitate was collected by filtration, successively washed with iPrOH (1×1 mL), water (4×2 mL) and ether (2×2 mL) to afford product (63 mg, 82%) as a white powder that had the following properties: m.p.=280-283° C.; LC/MS (ESI+): 443 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 9.25 (s, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.55 (d, 1H, J=8.6), 7.17 (d, 1H, J=8.3), 7.06 (s, 1H), 6.77 (s, 1H), 6.56 (d, 1H, J=8.6), 4.17 (m, 1H), 3.19 (s, 3H), 2.65 (m, 2H), 2.41 (m, 1H), 2.16 (m, 2H), 2.04 (m, 3H), 1.90-1.65 (m, 3H), 1.45 (m, 1H), 1.40-1.15 (m, 3H).
Reaction SMILES: O.[OH-].[Li+].[CH3:4][C:5]1([C:41]([O:43]C)=[O:42])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:14][C:15](=[O:40])[CH:16]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:27]3[C:32](=[O:33])[CH2:31][O:30][C:29]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[N:28]3)=[CH:22][CH:21]=2)[CH:17]([CH3:19])[CH3:18])[CH2:6]1.Cl>C1COCC1.O>[CH3:4][C:5]1([C:41]([OH:43])=[O:42])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:14][C:15](=[O:40])[CH:16]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:27]3[C:32](=[O:33])[CH2:31][O:30][C:29]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[N:28]3)=[CH:22][CH:21]=2)[CH:17]([CH3:19])[CH3:18])[CH2:6]1
Reactant: COC(=O)C1(C)Cc2cccc(NC(=O)C(c3ccc(CN4N=C(c5ccccc5)OCC4=O)cc3)C(C)C)c2C1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)C(C(=O)Nc1cccc2c1CC(C)(C(=O)O)C2)c1ccc(CN2N=C(c3ccccc3)OCC2=O)cc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
9.1 mg (0.22 mmol) of lithium hydroxide monohydrate were added to a solution of 60 mg (0.11 mmol) of methyl 2-methyl-4-[(3-methyl-2-{-4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}butanoyl)amino]-2,3-dihydro-1H-indene-2-carboxylate (Example 136A) in 2 ml of THF and 2 ml of water, and the mixture was stirred at 60° C. for 8 h. The reaction mixture was then adjusted to pH 4 with 1 M hydrochloric acid and concentrated to dryness under reduced pressure. The crude product obtained was purified by flash chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1→4:1→1:1 or dichloromethane/methanol 10:1). This gave 43 mg (0.08 mmol, 74% of theory) of the title compound.
Reaction SMILES: [CH3:1][O:2]/[N:3]=[C:4](/[C:35]1[N:36]=[C:37]([NH:40][C:41]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[S:38][CH:39]=1)\[C:5]([NH:7][CH:8]1[C:33](=[O:34])[N:10]2[C:11]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[C:12]([CH2:15][Cl:16])[CH2:13][S:14][C@H:9]12)=[O:6].ClC1C=CC=C(C(OO)=[O:68])C=1>C1C=CC=CC=1>[CH3:1][O:2]/[N:3]=[C:4](/[C:35]1[N:36]=[C:37]([NH:40][C:41]([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[S:38][CH:39]=1)\[C:5]([NH:7][CH:8]1[C:33](=[O:34])[N:10]2[C:11]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[O:18])=[C:12]([CH2:15][Cl:16])[CH2:13][S:14](=[O:68])[C@H:9]12)=[O:6]
Reactant: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CCl)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: c1ccccc1
Product: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CCl)CS(=O)[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.5 g (2.97 mmol) of benzhydryl 7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate was dissolved in 25 ml of benzene, and 640 mg (3.27 mmol) of m-chloroperbenzoic acid was added under cooling with ice. The mixture was stirred at room temperature for 1 hour. The reaction solution was poured into ice water, and extracted with ethyl acetate. The extracted solution was washed with a 5% sodium bisulfite aqueous solution and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure, whereby the above identified compound was obtained as an oily substance.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=2)=[C:4]([N+:18]([O-:20])=[O:19])[CH:3]=1.[CH2:21]([NH2:24])[CH2:22][CH3:23]>>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:15]=[CH:14][C:10]([C:11]([NH:24][CH2:21][CH2:22][CH3:23])=[O:12])=[CH:9][CH:8]=2)=[C:4]([N+:18]([O-:20])=[O:19])[CH:3]=1
Reactant: CCCN
Reactant: O=C(Cl)c1ccc(Oc2ccc(Cl)cc2[N+](=O)[O-])cc1
Product: CCCNC(=O)c1ccc(Oc2ccc(Cl)cc2[N+](=O)[O-])cc1
Yield: 95.2 %

Procedure:
The product from Example 126c (1.0 g, 3.2 mmol) was reacted with propan-1-amine (568 mg, 9.61 mmol) for 12 h following the procedure from Example 126d giving the title compound (1.02 g, 100%).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[N:12]=2)=[C:7]([OH:9])[CH:8]=1.[Na].[I-].[Na+].[NH4+].[Cl-].[CH3:23][OH:24]>>[F:17][C:13]1[N:12]=[C:11]([O:10][C:6]2[CH:5]=[CH:4][C:3]([CH2:2][O:24][CH3:23])=[CH:8][C:7]=2[OH:9])[CH:16]=[CH:15][CH:14]=1
Reactant: CO
Reactant: Oc1cc(CCl)ccc1Oc1cccc(F)n1
Agent: [Cl-]
Agent: [I-]
Agent: [NH4+]
Product: COCc1ccc(Oc2cccc(F)n2)c(O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 5-(chloromethyl)-2-[(6-fluoropyridin-2-yl)oxy]phenol (50 mg; 0.20 mmol), under argon, in methanol (1 mL) was added sodium methoxylate (3.94 mmol; 22 mg) and sodium iodide (0.07 mmol; 10 mg). The reaction mixture was allowed to stir at room temperature overnight. The reaction was hydrolysed with saturated NH4Cl (5 mL), extracted with ethyl acetate (3*2 mL), and washed with 5 mL of satured NaHCO3. Combined organic phases were dried over Na2SO4, concentrated in vacuo, the title compound (49 mg; 100%) was prepared as a light yellow oil without further purification.
Reaction SMILES: C(O[C@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.C[Si]([N:32]=[N+:33]=[N-:34])(C)C.[Sn](Cl)(Cl)(Cl)Cl>C(Cl)Cl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][C@@H:5]1[N:32]=[N+:33]=[N-:34])(=[O:10])[CH3:9]
Reactant: CC(=O)OC[C@H]1O[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@H](N=[N+]=[N-])[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 82 %

Procedure:
1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (5.00 g, 12.8 mmol) was dissolved in 10-15 mL dry CH2Cl2 under an inert atmosphere. Trimethylsilyl azide (4.24 mL, 32.1 mmol) and tin (IV) chloride (0.75 mL, 6.41 mmol) were added, and the reaction was stirred for 18 hours at room temperature. The reaction mixture was diluted with CH2Cl2 (30 mL) and washed twice with saturated NaHCO3 (20 mL) and with brine (20 mL). The organic phase was dried, filtered and concentrated to leave 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl azide as a white solid (3.92 g, 82%). 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl azide (0.30 g, 80 mmol) was then dissolved in dry THF (15 mL), and Pd/C was added (˜5%) to this solution. The mixture was stirred under H2 overnight. TLC revealed the reduction was completed (Rfazide=0.80, Rfamine=0.10). In a separate flask, compound 23 (0.17 g, 0.30 mmol) and 0.5 M HBTU in DMF (1.20 mL, 0.60 mmol) were combined, followed by the addition of DMF (˜2 mL) and DIEA (104 μL, 0.60 mmol). This solution was then added to the reaction flask, and the reaction mixture was stirred under N2 overnight. The resulting suspension was filtered through celite which was washed well with ethyl acetate (˜100 mL), and the filtrate was washed with 5 M HCl (50 mL), saturated NaHCO3 (2×50 mL), and brine (1×50 mL). The organic solution was dried over magnesium sulfate, filtered, and concentrated. The residue was purified using a silica gel column chromatography with 10% MeOH/DCM to yield V (0.16 g, 59.33). 1H NMR δ (CDCl3) 0.78 (3H, t, J=7 Hz), 1.16-1.23 (32H, brm), 1.35 (2H, m) 1.52 (2H, m) 1.57 (6H, brs), 1.86 (6H, brs), 1.91-2.00 (15H, m), 2.14 (2H, m), 2.99 (2H, t, J=7 Hz), 3.75 (2H, m), 3.95-4.07 (3H, m), 4.15-4.29 (4H, m), 4.43-4.38 (1H, m) 4.80 (1H, dd, J=5, 11 Hz), 4.84-4.89 (2H, m), 4.95-5.02 (3H, m), 5.12-5.24 (3H, m), 5.35 (1H, d, J=3 Hz), 5.47 (1H, t, J=9.8 Hz), 6.28 (1H, dd, J=7.6, 19 Hz), 6.60 (1H, d, J=9.3 Hz), 7.18 (1H, d, J=9.1 Hz), 7.34 (1H, d, J=9.1 Hz). LC-MS (ESI) m/z calcd for C47H78N4O12 [M+H]+ 891.56. found [M+H]+ 891.69.
Reaction SMILES: [C:1]1([CH2:7][C:8]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[NH:16][C:15](=[O:20])[C:14]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)=[N:13]3)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[H][H].[Pd].C(O)(=O)C>[CH2:8]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])[C:14]([C:21]1[S:22][CH:23]=[CH:24][CH:25]=1)=[N:13]2)[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: [H][H]
Reactant: O=C(Cc1ccccc1)c1ccc2[nH]c(=O)c(-c3cccs3)nc2c1
Agent: [Pd]
Solvent: CC(=O)O
Product: O=c1[nH]c2ccc(CCc3ccccc3)cc2nc1-c1cccs1

Procedure:
The quinoxalin-2-one of the present example is prepared with 6-Phenylacetyl-3-thiophen-2-yl-1H-quinoxalin-2-one from Example 46 via treatment with H2/Pd—C in the presence of acetic acid to form the 6-phenethyl compound.
Reaction SMILES: C(N(CC)CCOC1C=CC(C([N:13]([CH2:34][CH3:35])[C:14]2[CH:19]=[C:18]([O:20]C)[CH:17]=[CH:16][C:15]=2[CH:22]2[CH2:31][CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:32]C)[CH:28]=3)[CH2:23]2)=O)=CC=1)C.[CH2:40]([N:42]([CH2:76][CH3:77])[CH2:43][CH2:44][O:45][C:46]1[CH:75]=[CH:74][C:49]([CH2:50]N(CC)C2C=C(OC)C=CC=2C2CCC3C(=CC=C(OC)C=3)C2)=[CH:48][CH:47]=1)[CH3:41]>>[CH2:76]([N:42]([CH2:40][CH3:41])[CH2:43][CH2:44][O:45][C:46]1[CH:47]=[CH:48][C:49]([CH2:50][CH2:35][CH2:34][NH:13][C:14]2[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][C:15]=2[CH:22]2[CH2:31][CH2:30][C:29]3[CH:28]=[C:27]([OH:32])[CH:26]=[CH:25][C:24]=3[CH2:23]2)=[CH:74][CH:75]=1)[CH3:77]
Reactant: CCN(CC)CCOc1ccc(C(=O)N(CC)c2cc(OC)ccc2C2CCc3cc(OC)ccc3C2)cc1
Reactant: CCN(CC)CCOc1ccc(CN(CC)c2cc(OC)ccc2C2CCc3cc(OC)ccc3C2)cc1
Product: CCN(CC)CCOc1ccc(CCCNc2cc(O)ccc2C2CCc3cc(O)ccc3C2)cc1

Procedure:
Synthesized from 4-(2-diethylaminoethoxy)-N-ethyl-N-[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]benzamide according to an analogous synthetic method to Example 337, [4-(2-diethylaminoethoxy)benzyl]ethyl[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amine (149 mg) was used according to an analogous synthetic method to Example 111 to provide the title compound (159 mg).