Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[C:5]([CH:6]=[O:7])=[CH:4][N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[F:14][C:15]([Si](C)(C)C)([F:17])[F:16]>CN(C)C=O>[F:14][C:15]([F:17])([F:16])[CH:6]([C:5]1[S:1][CH:2]=[N:3][CH:4]=1)[OH:7]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: O=Cc1cncs1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OC(c1cncs1)C(F)(F)F
Yield: 72.7 %

Procedure:
According to Reference Example 8-2, by use of thiazole-5-carbaldehyde (300 mg, 2.65 mmol) dissolved in N,N-dimethylformamide (4.5 mL), potassium carbonate (73 mg, 0.53 mmol) and (trifluoromethyl)trimethylsilane (0.470 mL, 3.18 mmol), the mixture was stirred and reacted at room temperature for 1 hour. Then, purification by preparative thin-layer chromatography (chloroform/methanol=15/1) was performed to give 2,2,2-trifluoro-1-(thiazol-5-yl)ethanol (Compound DL) (353 mg, yield: 73%).
Reaction SMILES: [H-].[Na+].C(N(CC)CC)C.[OH:10][CH2:11][CH2:12][N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].[Br:22][C:23]1[CH:28]=[CH:27][C:26](F)=[C:25]([C:30]([F:33])([F:32])[F:31])[CH:24]=1>CN(C=O)C.CCOC(C)=O>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([O:10][CH2:11][CH2:12][N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[C:25]([C:30]([F:31])([F:32])[F:33])[CH:24]=1
Reactant: CN(CCO)C(=O)OC(C)(C)C
Reactant: Fc1ccc(Br)cc1C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN(CCOc1ccc(Br)cc1C(F)(F)F)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Sodium hydride (247 mmol, 9.88 g) was stirred in DMF (100 ml) at room temperature. triethylamine (165 mmol, 22.88 ml, 16.66 g) was added. tert-butyl 2-hydroxyethyl(methyl)carbamate (173 mmol, 30.3 g) was added dropwise in DMF. 4-bromo-1-fluoro-2-(trifluoromethyl)benzene (165 mmol, 40 g) was added in one portion and the reaction was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with water. The organic was dried over sodium sulfate and concentrated in vacuo. The resulting residue was purified by flash chromatography eluting with heptane—60/40 heptane/EtOAc. Fractions were collected and combined to afford tert-butyl 2-(4-bromo-2-(trifluoromethyl)phenoxy)-ethyl(methyl)carbamate. (18.44 g)
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([CH:19]=[O:20])=[CH:16][CH:17]=3)[CH:12]=[C:11]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].[Cl-].[NH4+]>C(O)C>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([CH2:19][OH:20])=[CH:16][CH:17]=3)[CH:12]=[C:11]2[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=Cc1ccc2c(c1)cc(-c1ccccc1)n2S(=O)(=O)c1ccccc1
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Product: O=S(=O)(c1ccccc1)n1c(-c2ccccc2)cc2cc(CO)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
To a suspension of 1-benzenesulfonyl-5-formyl-2-phenylindole (224 mg) in ethanol (2.5 mL) was added sodium borohydride (11.7 mg), and the mixture was stirred at room temperature for one hour. A saturated aqueous ammonium chloride solution was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (173 mg).
Reaction SMILES: [N:1]1([CH:6]([C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=2)[CH2:7][CH3:8])[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][C:27](Cl)=[O:28]>ClCCCl>[N:1]1([CH:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:27](=[O:28])[CH2:26][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH3:19])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=2)[CH2:7][CH3:8])[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: Cc1ccccc1CC(=O)Cl
Reactant: CCC(c1ccc(N)c([N+](=O)[O-])c1)n1ccnc1
Solvent: ClCCCl
Product: CCC(c1ccc(NC(=O)Cc2ccccc2C)c([N+](=O)[O-])c1)n1ccnc1
Temperature: 0 °C
Yield: 89.3 %

Procedure:
To a stirred and cooled (0° C.) solution of 7 parts of 4-[1-(1H-imidazol-1-yl)propyl]-2-nitrobenzenamine in 126 parts of 1,2-dichloroethane were added 9.6 parts of 2-methylbenzeneacetyl chloride. After stirring for 12 hours at room temperature, the reaction mixture was poured into ice water and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated in vacuo. The oily residue was purified by column chromatography over silica gel using a mixture of dichloromethane and methanol (98:2 by volume) as eluent. The eluent of the desired fraction was evaporated, yielding 9.6 parts (89.3%) of N-[4-[1-(1H-imidazol-1-yl)propyl]-2-nitrophenyl]-2-methylbenzeneacetamide; mp. 122° C. (interm. 48).
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:19]([CH2:20][CH2:21][C@:3]12[CH3:4])[C@:16]1([CH2:17][OH:18])[C:11](=[CH:12][C:13](=[O:23])[CH2:14][C@@H:15]1[CH3:22])[CH2:10][CH2:9]3.[BH4-].[Na+].C(O)(=O)C>C(O)C>[CH3:22][C@@H:15]1[C@@:16]2([CH2:17][OH:18])[C:11]([CH2:10][CH2:9][C@@H:8]3[C@@H:19]2[CH2:20][CH2:21][C@@:3]2([CH3:4])[C@H:5]3[CH2:6][CH2:7][C@@H:2]2[OH:1])=[CH:12][C@@H:13]([OH:23])[CH2:14]1
Reactant: C[C@H]1CC(=O)C=C2CC[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]3[C@]21CO
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: C[C@H]1C[C@H](O)C=C2CC[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]3[C@]21CO
Temperature: 25 °C
Reaction time: 4 h

Procedure:
17β,19-Dihydroxy-1α-methyl-4-androsten-3-one is dissolved in ethanol and sodium borohydride is added slowly under nitrogen. After stirring at room temperature for 4 hours, the solution is poured onto ice water containing a few drops of acetic acid. The solid which forms is filtered and recrystallized from ethanol to yield 1α-methyl-4-androstene-3β,17β,19-triol.
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:16]=[CH:15][C:9]([C:10]([CH2:12][C:13]#[N:14])=[O:11])=[CH:8][CH:7]=1)(=[O:4])=[O:3].[CH2:17]([O:19][CH:20](OC(=O)C)OCC)[CH3:18]>C(#N)C>[CH2:17]([O:19][CH:20]=[C:12]([C:10](=[O:11])[C:9]1[CH:8]=[CH:7][C:6]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:16][CH:15]=1)[C:13]#[N:14])[CH3:18]
Reactant: CCOC(OCC)OC(C)=O
Reactant: CS(=O)(=O)Nc1ccc(C(=O)CC#N)cc1
Solvent: CC#N
Product: CCOC=C(C#N)C(=O)c1ccc(NS(C)(=O)=O)cc1
Temperature: 25 °C
Yield: 82.1 %

Procedure:
To a slurry of 4-methylsulfonamidobenzoylacetonitrile (7.0 g) in acetonitrile (70 ml), diethoxymethylacetate (16.2 g) was added and the mixture heated at reflux for 30 minutes. The mixture was cooled to room temperature and filtered. The filtrate was poured into 600 ml diethyl ether, after which 800 ml ligroin P950 was added with rapid stirring. A light yellow oil formed in droplets, which spontaneously crystallized. The crystalline product was collected by filtration, washed with ligroin P950, and dried to yield 7.1 g of 2-(ethoxymethylidene)-2-(4'-methylsulfonamidobenzoyl)-acetonitrile.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl.CO.[OH-].[NH4+]>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(Nc3cccc(S(C)(=O)=O)c3)nc12
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(Nc3cccc(S(C)(=O)=O)c3)nc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.9 %

Procedure:
To a solution of N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (61 mg, 118 mol) in dichloromethane (1.8 mL) was added trifluoroacetic acid (269 mg, 182 μL, 2.36 mmol) and the mixture stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue obtained diluted with dichloromethane (1.8 mL), methanol (0.9 mL) and ammonium hydroxide (0.25 mL) and stirred at room temperature for 1 h. The mixture was concentrated and triturated with water. The solid was collected by filtration and washed with water and ether. Purification by chromatography (silica, GRADIENT UNKNOWN dichloromethane/methanol/0.5% ammonium hydroxide) gave N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (26 mg, 67.1 mol, 57%) as a yellow solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.42 (s, 1H), 9.87 (s, 1H), 8.33 (d, J=8.2, 1 H), 8.05 (d, J=3.4, 1 H), 8.03 (s, 1H), 7.79 (t, J=2.0, 1 H), 7.68 (s, 1H), 7.54 (t, J=8.0, 1 H), 7.47 (d, J=7.7, 1 H), 3.21 (s, 3H), 1.42 (s, 9H); MS (EI/CI) m/z: 388.2 [M+H].
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=O)C=1.[Cl:12][CH2:13][C:14]1[N:15]([CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:35])[CH:32]([CH3:34])[CH3:33])[C:16]2[C:25]3[N:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:19]=[CH:18][C:17]=2[N:26]=1.[OH-].[NH4+:37].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.[Cl-].[Na+].O>[NH2:37][C:18]1[C:17]2[N:26]=[C:14]([CH2:13][Cl:12])[N:15]([CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:35])[CH:32]([CH3:33])[CH3:34])[C:16]=2[C:25]2[N:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N:19]=1
Reactant: CC(C)C(=O)NCCCn1c(CCl)nc2cnc3cccnc3c21
Reactant: [NH4+]
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Cl-]
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(C)C(=O)NCCCn1c(CCl)nc2c(N)nc3cccnc3c21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
mCPBA (0.985 g, 5.71 mmol) was added to a suspension of N-{3-[2-(chloromethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propyl}-2-methylpropanamide (1.41 g, 4.08 mmol) in chloroform (20 mL). The reaction mixture was allowed to stir for 4 hours at room temperature. Concentrated ammonium hydroxide (5 mL) followed by p-toluenesulfonyl chloride (0.854 g, 4.48 mmol) were added and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with chloroform (25 mL) and brine (40 mL) and transferred to a separatory funnel. The aqueous layer was extracted with chloroform (20 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated to afford a tan solid. Trituration with methanol and isolation by filtration afforded 0.670 g of N-{3-[4-amino-2-(chloromethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propyl}-2-methylpropanamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[C:8]([CH3:17])[C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([C:18]([OH:20])=[O:19])[CH:4]=1.[Li]N1C(C)(C)CCCC1(C)C.[CH3:32][Si:33](Cl)([CH3:35])[CH3:34].[OH-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[C:8]([CH2:17][Si:33]([CH3:35])([CH3:34])[CH3:32])[C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([C:18]([OH:20])=[O:19])[CH:4]=1
Reactant: C[Si](C)(C)Cl
Reactant: COc1cc2c(OC)cc(C(=O)O)cc2c(C)c1OC
Agent: [Li]N1C(C)(C)CCCC1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1cc2c(OC)cc(C(=O)O)cc2c(C[Si](C)(C)C)c1OC
Temperature: -78 °C
Reaction time: 1 h
Yield: 88.1 %

Procedure:
4,6,7-Trimethoxy-8-methyl-2-naphthoic acid (1) (0.276 g, 1 mmol) is added at −78° C. to a mixture containing the base LTMP (4.2 mmol) and TMSCl (0.998 mL, 5.7 mmol) in anhydrous THF (10 mL). The reaction mixture is stirred at −78° C. for 1 h then gradually heated to ambient temperature over 3 h. After hydrolysis, the reaction mixture is treated with a solution of 2M NaOH (pH 10). The aqueous phase is washed with ethyl ether (2×15 mL), acidified with 2M HCl (pH 1-2) then extracted with dichloromethane (3×20 mL). The combined organic phases are dried over MgSO4, filtered, then concentrated under reduced pressure. The residue is purified by recrystallization (cyclohexane/ethyl acetate) to give 4,6,7-trimethoxy-8-((trimethylsilyl)methyl)-2-naphthoic acid (2) (0.307 g, 88%). 1H NMR (200 MHz, CDCl3): 8.37 (s, 1H), 7.44 (s, 1H), 7.40 (s, 1H), 4.07 (s, 3H, OCH3), 4.03 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 2.63 (s, 2H, CH2), 0.02 (s, 9H, Si(CH3)3). SMHR, [M+H]+ calculated for C18H25O5Si: 349.1471. Found: 349.1468.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH2:11])=[S:10])=[CH:4][C:3]=1[O:12][CH3:13].Br[CH2:15][C:16](=O)[C:17]([OH:19])=[O:18]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][CH:15]=[C:16]([C:17]([OH:19])=[O:18])[N:11]=2)=[CH:4][C:3]=1[O:12][CH3:13]
Reactant: O=C(O)C(=O)CBr
Reactant: COc1cc(NC(N)=S)ccc1Cl
Solvent: CCO
Product: COc1cc(Nc2nc(C(=O)O)cs2)ccc1Cl
Temperature: 60 °C

Procedure:
A mixture of 7.8 g (36 mmol) 1-(4-chloro-3-methoxyphenyl)-thiourea, and 6.2 g (36 mmol) bromopyruvic acid in 80 ml ethanol was heated to 60° C. for 1 h. The precipitate was filtered off and washed with small portions of cold ethanol to yield after drying 10.0 g (98%) of the title compound as crystalline solid.
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[S:8][CH2:9][CH2:10][CH2:11][CH:12]([C:18]([OH:20])=[O:19])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])C=CC=CC=1.C([SiH](C(C)C)C(C)C)(C)C>C(Cl)Cl>[SH:8][CH2:9][CH2:10][CH2:11][CH:12]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])[C:18]([OH:20])=[O:19]
Reactant: O=C(O)CCC(CCCSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)O
Agent: CC(C)[SiH](C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(O)CCC(CCCS)C(=O)O
Reaction time: 1 h
Yield: 69 %

Procedure:
2.46 mmol of 6-[(triphenylmethyl)thio]-1,3-hexanedicarboxylic acid (IV) (1.1 g) with 5 mmol triisopropylsilane (0.79 g) was dissolved in a mixture of 3 ml CH2Cl2/3 ml trifluoroacetic acid and left to stand at room temperature for 1 hour. The mixture was then evaporated to dryness and washed 3× with hexane. The remaining oily residue was dissolved in water, filtered and lyophilized to yield 0.35 g of 2-(3-sulfanylpropyl) pentanedioic acid (V) (76%), 13C-NMR (MeOH) δ 25.2(t), 28.8(t), 32.4(t), 33.0(t), 33.2(t), 45.9(d), 177.2(s), 179.6(s).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>>[CH3:24][O:23][C:13]1[C:11]2[N:12]=[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:25]=[CH:26][N:27]=[C:2]([NH:34][CH2:35][CH2:36][N:37]4[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]4)[CH:3]=3)[S:9][C:10]=2[C:16]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:15][CH:14]=1
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(Br)c3)nc12
Reactant: NCCN1CCCCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(NCCN4CCCCC4)c3)nc12

Procedure:
From 2-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide with cesium carbonate and 1-(2-aminoethyl)-piperidine. ES-MS m/e (%): 497 (M+H+, 100).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:21])=[N:8][C:9]([Cl:20])=[C:10]([N+:17]([O-:19])=[O:18])[C:11]=1[NH:12]C(C)(C)C)=[O:5])[CH3:2]>CO>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:21])=[N:8][C:9]([Cl:20])=[C:10]([N+:17]([O-:19])=[O:18])[C:11]=1[NH2:12])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(C)nc(Cl)c([N+](=O)[O-])c1NC(C)(C)C
Solvent: CO
Product: CCOC(=O)c1c(C)nc(Cl)c([N+](=O)[O-])c1N
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
31.6 g. of 6-chloro-4[(1,1-dimethylethyl)amino]-2-methyl-5-nitropyridine-3-carboxylic acid ethyl ester (0.1 mol.) are heated with stirring at 250°-260° for 5 minutes. The dark oil is cooled to room temperature and 50 ml. of methyl alcohol are added. 18.2 g. of 4-amino-6-chloro-2-methyl-5-nitropyridine-3-carboxylic acid ethyl ester crystallize on cooling (70%), m.p. 89-91° (methanol).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:10]=[C:11]([C:25](=[O:27])[CH3:26])[CH:12]=[N:13][C:14]=2[NH:15][C:16]2[CH:17]=[N:18][C:19]([O:23][CH3:24])=[C:20]([F:22])[CH:21]=2)[N:3]=1.[BH4-].[Na+]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:10]=[C:11]([CH:25]([OH:27])[CH3:26])[CH:12]=[N:13][C:14]=2[NH:15][C:16]2[CH:17]=[N:18][C:19]([O:23][CH3:24])=[C:20]([F:22])[CH:21]=2)[N:3]=1
Reactant: COc1ncc(Nc2ncc(C(C)=O)cc2-c2nc(C)nc(N)n2)cc1F
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ncc(Nc2ncc(C(C)O)cc2-c2nc(C)nc(N)n2)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
1-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (250 mg, 0.677 mmol) was dissolved in THF (1.35 mL), sodium borohydride (128 mg, 3.38 mmol) was added, and the resulting mixture was stirred at ambient temperature for 2 h. The reaction mixture was then quenched with water and added to a separatory funnel The reaction mixture was then partitioned between EtOAc (100 mL) and ammonium chloride (saturated, aqueous). The organic layer was separated, washed 2 times with 75 mL of ammonium chloride (saturated, aqueous), dried over sodium sulfate, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0% to 5% (2 M ammonia in MeOH)/DCM) gave the title compound (40% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.90 (s, 1H) 8.87 (s, 1H) 8.34 (d, J=2.15 Hz, 1H) 8.20-8.30 (m, 1H) 8.05 (d, J=1.76 Hz, 1H) 5.41 (br. s., 2H) 4.95 (q, J=6.52 Hz, 1H) 4.03 (s, 3H) 2.57 (s, 3H) 1.83 (br. s., 1H) 1.58 (br. s., 3H). m/z (ESI, +ve ion) 372.0 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:18]=[C:19]([N+:21]([O-])=O)[CH:20]=2)[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:5]=[CH:4][N:3]=1.[H][H]>CO.[Pd]>[NH2:21][C:19]1[CH:18]=[C:10]([CH:9]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=2)[CH:20]=1)[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]
Reactant: Cc1cc(-c2cc(C(=O)OC(C)(C)C)cc([N+](=O)[O-])c2)ccn1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: Cc1cc(-c2cc(N)cc(C(=O)OC(C)(C)C)c2)ccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
A mixture of tert-butyl 3-(2-methylpyridin-4-yl)-5-nitrobenzoate (1.5 g, 4.8 mmol) and 300 mg of 10% wet Pd/C (˜50% H2O) in 25 mL of methanol under a balloon of hydrogen was allowed to stir at room temperature overnight. Upon completion, the mixture was concentrated and the residue was dried to give 1.31 g of tert-Butyl 3-amino-5-(2-methylpyridin-4-yl)benzoate 49.1B. LCMS (ES+) m/z 285.
Reaction SMILES: C1(P(O[C:16]2[C@H:17]([CH3:40])[C@@H:18]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]3[C:20]=2[C:21]([O:23]CC2C=CC([N+]([O-])=O)=CC=2)=[O:22])(C2C=CC=CC=2)=O)C=CC=CC=1.[SH:41][C@@H:42]1[CH2:46][N:45](C(OCC2C=CC([N+]([O-])=O)=CC=2)=O)[C@H:44]([C:60](=[O:81])[NH:61][CH2:62][CH2:63][N:64](C(OCC2C=CC([N+]([O-])=O)=CC=2)=O)[C:65]([NH2:67])=[NH:66])[CH2:43]1>>[NH:64]([CH2:63][CH2:62][NH:61][C:60]([C@@H:44]1[CH2:43][C@H:42]([S:41][C:16]2[C@H:17]([CH3:40])[C@@H:18]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]3[C:20]=2[C:21]([OH:23])=[O:22])[CH2:46][NH:45]1)=[O:81])[C:65]([NH2:67])=[NH:66]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@H]12
Reactant: N=C(N)N(CCNC(=O)[C@@H]1C[C@H](S)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)OCc1ccc([N+](=O)[O-])cc1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(=O)NCCNC(=N)N)C3)[C@H](C)[C@H]12

Procedure:
A procedure similar to that described in Example 101 was repeated, but using 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphoryloxy)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (prepared as described in Preparation 123) and (2S,4S)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)-2-[2-(4-nitrobenzyloxycarbonylguanidino)ethylcarbamoyl]pyrrolidine (prepared as described in Preparation 102) as starting materials, in relative proportions similar to those used in that Example, to obtain the title compound.
Reaction SMILES: [CH3:1][C:2]([CH3:21])([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:8]=1)[C:3]([OH:5])=[O:4].[CH3:22]O>OS(O)(=O)=O.O>[CH3:1][C:2]([CH3:21])([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:8]=1)[C:3]([O:5][CH3:22])=[O:4]
Reactant: CO
Reactant: CC(C)(Cc1cccc(OCc2ccccc2)c1)C(=O)O
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)C(C)(C)Cc1cccc(OCc2ccccc2)c1
Yield: 50 %

Procedure:
A solution of 2,2-dimethyl-3-(3-benzyloxyphenyl)propionic acid (400 mg, 1.4 mmole) in 20 mL of MeOH and 0.5 mL conc. H2SO4 was refluxed for 18 hours. The reaction was cooled, diluted with H2O and extracted with Et2O. The extracts were washed with H2O, three times with aqueous NaHCO3, dried, and the solvent evaporated. The residue was chromatographed over a silica gel column, and elution with a mixture of CH2Cl2, hexane and MeOH (50:50:1) gave the titled compound, 208 mg (50% yield). MS (ESI) 299 (MH+).
Reaction SMILES: C(=O)([O-])[O-].[K+:5].[K+].[CH2:7]([N:9]1[C:14]2[N:15]=[C:16]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[N:17]=[CH:18][C:13]=2[C:12](=[O:25])[C:11]([C:26]([OH:28])=[O:27])=[CH:10]1)[CH3:8].C(O)C>O>[CH2:7]([N:9]1[C:14]2[N:15]=[C:16]([N:19]3[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]3)[N:17]=[CH:18][C:13]=2[C:12](=[O:25])[C:11]([C:26]([O-:28])=[O:27])=[CH:10]1)[CH3:8].[K+:5]
Reactant: CCn1cc(C(=O)O)c(=O)c2cnc(N3CCNCC3)nc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CCn1cc(C(=O)[O-])c(=O)c2cnc(N3CCNCC3)nc21
Yield: 61.6 %

Procedure:
To a solution of potassium carbonate (2.76 g) in 60 ml of water was added 6.06 g of 5,8-dihydro-8-ethyl-2-(1-piperazinyl)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid. The resulting mixture was heated on a steam bath until it became a clear solution. Ethanol was added to the solution, and the mixture was then kept below room temperature by external cooling to yield the precipitate, which was collected and washed with ethanol. There is obtained 4.2 g of the product m.p. above 300°C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])=[C:8]([OH:10])[CH:9]=1)([O-:3])=[O:2].Cl.Cl[CH2:20][CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.C([O-])([O-])=O.[K+].[K+].CC(C)=O>CCOC(C)=O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:11]([F:16])([F:17])[C:12]([F:13])([F:14])[F:15])=[C:8]([CH:9]=1)[O:10][CH2:20][CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(O)c1
Reactant: ClCCN1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: O=[N+]([O-])c1ccc(C(F)(F)C(F)(F)F)c(OCCN2CCCC2)c1
Temperature: 70 °C

Procedure:
A flask was charged with 5-nitro-2-pentafluoroethyl-phenol (3.67 g, 14.2 mmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (9.71 g, 57.1 mmol), K2CO3 (7.9 g, 57.1 mmol), and acetone (20 mL). The reaction was heated at 70° C. for 3 days. The acetone evaporated from the reaction. No reaction was observed, so the organic material was recovered by extraction of water with EtOAc. The organic layer was dried with MgSO4, filtered and concentrated in vacuo. This crude mixture was dissolved in DMF (20 mL), combined with K2CO3 (5.9 g, 42.1 mmol) and heated to 70° C. for 24 h. The reaction mixture was cooled to RT, taken up in EtOAc and washed with 2 N NaOH, and brine. The organic layer was dried with MgSO4, filtered and concentrated in vacuo. The aqueous layer was acidified, extracted with EtOAc and dried with MgSO4, filtered, concentrated in vacuo and combined with the other portion. The title compound was purified by column chromatography using 0-10% MeOH in CH2Cl2.