Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.Cl.[CH3:11][NH:12][O:13][CH3:14].CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(Cl)Cl>[CH3:14][O:13][N:12]([CH3:11])[C:7]([CH:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1)=[O:9]
Reactant: O=C(O)C1CCOCC1
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)C1CCOCC1
Temperature: 29 °C
Reaction time: 24 h
Yield: 59.2 %

Procedure:
To a suspension of tetrahydro-2H-pyran-4-carboxylic acid (9.0 g, 69.2 mmol) in CH2Cl2 (300 mL) was added N,O-dimethylhydroxylamine hydrochloride (8.05 g, 83.0 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (20.0 g, 103.8 mmol) and triethylamine (17.5 g, 173.0 mmol) at 29° C. under N2. The reaction was stirred at 29° C. for 24 hrs. Then the mixture was filtered and the filtrate was washed with 1M HCl and saturated aqueous NaHCO3. The organic layer was concentrated in vacuo to give N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (7.1 g, 59.7%) as a yellow oil. 1H NMR (CDCl3, 400 M Hz) δ 4.02-3.98 (m, 2H), 3.69 (s, 3H), 3.47-3.41 (m, 2H), 3.17 (s, 3H), 2.90 (t, J=11.6 Hz, 3H), 1.90-1.82 (m, 2H), 1.81-1.62 (m, 2H).
Reaction SMILES: [BH4-].[Na+].[C:3]([O:7][C:8](=[O:27])[CH:9]([CH3:26])[C:10](=[O:25])[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)([CH3:6])([CH3:5])[CH3:4].Cl>CO>[C:3]([O:7][C:8](=[O:27])[CH:9]([CH3:26])[CH:10]([OH:25])[CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:17][CH:18]=1)([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C(=O)CCc1ccc(-c2ccccc2)cc1)C(=O)OC(C)(C)C
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C(=O)OC(C)(C)C)C(O)CCc1ccc(-c2ccccc2)cc1
Yield: 95.7 %

Procedure:
Sodium borohydride (17 mg, 0.44 mmol) was added to a stirred solution of 5-biphenyl-4-yl-2-methyl-3-oxo-pentanoic acid tert-butyl ester (Intermediate 6, 135 mg, 0.399 mmol) in methanol (3 mL) at 0° C. under nitrogen. After stirring for 1 hour 1 M hydrochloric acid (5 mL) was added and the crude reaction mixture extracted with diethyl ether (3×5 mL). The organic phases were combined, washed with brine (5 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure to give the title compound (130 mg, 96%) as a colourless gum, mixture of diastereoisomers. LC/MS: 3.72 min; z/e 341, calcd (M+1) 341.1H NMR (400 MHz: CDCl3): 7.59 (2 H), 7.51 (2 H), 7.42 (2 H), 7.28 (3 H), 4.21, 3.90, 3.65, 2.89, 2.75, 1.81, 1.69, 1.55, 1.44, 1.30, 1.18.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.I[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc2cc[nH]c2c1
Reactant: Ic1ccccc1
Product: Cc1ccc2ccn(-c3ccccc3)c2c1

Procedure:
Prepared by Procedure C and Scheme O using 6-methyl-1H-indole and iodobenzene: ESMS m/e: 208.0 (M+H)+.
Reaction SMILES: Br[CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.[C-:13]#[N:14].[K+]>CN(C=O)C>[CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[CH:12][C:3]=1[CH2:2][C:13]#[N:14]
Reactant: [C-]#N
Reactant: BrCc1ccc2ccccc2c1
Agent: [K+]
Solvent: CN(C)C=O
Product: N#CCc1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 65.8 %

Procedure:
2-Bromomethyinaphthalene (5.00 g, 23 mmol) was dissolved in N,N'-dimethylformamide (50 ml) and potassium cyanide (2.95 g, 45 mmol) was added and the resulting mixture was stirred at room temperature for 16 hours. The supematant was decanted and partitioned between water (100 ml) and diethyl ether (2×75 ml). The combined organic phases were washed with water (100 ml), dried (MgSO4), filtered and evaporated in vacuo affording 2.53 g (67%) of 2-naphtylacetonitrile as a solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:26])=[CH:4][C:5]([Cl:25])=[C:6]([N:8]2[C:13](=[O:14])[N:12]([CH3:15])[C:11](=[O:16])[N:10]([CH2:17][C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])[C:9]2=[O:24])[CH:7]=1.[F:27][C:28]1[CH:38]=[CH:37][CH:36]=[C:30]2[C:31]([O:33][C:34](=O)[C:29]=12)=[O:32]>C(O)(=O)C>[Cl:25][C:5]1[CH:4]=[C:3]([F:26])[C:2]([N:1]2[C:34](=[O:33])[C:29]3=[C:28]([F:27])[CH:38]=[CH:37][CH:36]=[C:30]3[C:31]2=[O:32])=[CH:7][C:6]=1[N:8]1[C:13](=[O:14])[N:12]([CH3:15])[C:11](=[O:16])[N:10]([CH2:17][C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])[C:9]1=[O:24]
Reactant: O=C1OC(=O)c2c(F)cccc21
Reactant: CC(C)OC(=O)Cn1c(=O)n(C)c(=O)n(-c2cc(N)c(F)cc2Cl)c1=O
Solvent: CC(=O)O
Product: CC(C)OC(=O)Cn1c(=O)n(C)c(=O)n(-c2cc(N3C(=O)c4cccc(F)c4C3=O)c(F)cc2Cl)c1=O
Temperature: 25 °C

Procedure:
A solution of isopropyl 3-(5-amino-2-chloro-4-fluorophenyl)tetrahydro-5-methyl-2,4,6-trioxo-s-triazine-1(2H)-acetate (1.0 g, 2.6 mmol) and 3-fluorophthalic anhydride (0.51 g, 3.1 mmol) in acetic acid is refluxed for 6 hours, stirred at room temperature for several days and poured onto ice. The resultant aqueous mixture is filtered to obtain a solid. The solid is dried and chromatographed (silica gel/2.5% ether in methylene chloride solution) to give the title product as a yellow foam, mp 119°-125° C.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH:5]1[S:9][C:8]2[C:10]([CH3:17])=[C:11]([OH:16])[C:12]([CH3:15])=[C:13]([CH3:14])[C:7]=2[O:6]1.[I-:18].[Na+].O>CC(C)=O>[OH:16][C:11]1[C:12]([CH3:15])=[C:13]([CH3:14])[C:7]2[O:6][CH:5]([CH2:4][CH2:3][CH2:2][I:18])[S:9][C:8]=2[C:10]=1[CH3:17]
Reactant: Cc1c(C)c2c(c(C)c1O)SC(CCCCl)O2
Reactant: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: Cc1c(C)c2c(c(C)c1O)SC(CCCI)O2

Procedure:
120 mg of 2-(3-chloropropyl)-5-hydroxy-4,6,7-trimethyl-1,3-benzoxathiole (prepared as described in Example 77) were dissolved in 2 ml of acetone, after which 660 mg of sodium iodide were added, and the reaction mixture was heated under reflux for 10 hours. The reaction mixture was cooled and then poured into water, and the resulting precipitate was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The ethyl acetate was distilled off under reduced pressure and the resulting crude product was purified in the same manner as described in (a), to give the title compound having the same Rf value and mass spectrum as the product of (a) above.
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:3]=1[C:4]([NH:6][C:7](=[O:24])[NH:8][C:9]1[C:10]([N:15]2[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=O)[CH2:17][CH2:16]2)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:5].C[N:32](C=O)C.[Cl-].[NH4+].CCN(C(C)C)C(C)C>O>[Cl:1][C:2]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:3]=1[C:4]([NH:6][C:7](=[O:24])[NH:8][C:9]1[C:10]([N:15]2[CH2:16][CH2:17][CH:18]([C:21]([NH2:32])=[O:23])[CH2:19][CH2:20]2)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:5]
Reactant: CN(C)C=O
Reactant: O=C(NC(=O)c1cc(F)c(F)cc1Cl)Nc1cccnc1N1CCC(C(=O)O)CC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: NC(=O)C1CCN(c2ncccc2NC(=O)NC(=O)c2cc(F)c(F)cc2Cl)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The mixture consisting of 50 mg of 3′-[3-(2-chloro-4,5-difluorobenzoyl)ureido]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid, 0.5 ml of DMF, 6.1 mg of ammonium chlorid, 40 μl of Hunig's base and 37.3 mg of Totu was stirred at room temperature for 2 hours. Afterwards, it was diluted with 5 ml of water and the mixture was stirred briefly. The precipitate was filtered of with suction and dried under reduced pressure.
Reaction SMILES: [F:1][C:2]1([F:14])[CH:9]2[CH2:10][C:5]3([CH2:12][OH:13])[CH2:6][CH:7]([CH2:11][CH:3]1[CH2:4]3)[CH2:8]2.[Cl:15][C:16]1[C:17](F)=[CH:18][C:19]([F:29])=[C:20]([CH:28]=1)[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O>[Cl:15][C:16]1[C:17]([O:13][CH2:12][C:5]23[CH2:10][CH:9]4[CH2:8][CH:7]([CH2:11][CH:3]([C:2]4([F:14])[F:1])[CH2:4]2)[CH2:6]3)=[CH:18][C:19]([F:29])=[C:20]([CH:28]=1)[C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22]
Reactant: OCC12CC3CC(C1)C(F)(F)C(C3)C2
Reactant: CC(C)(C)OC(=O)c1cc(Cl)c(F)cc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)c1cc(Cl)c(OCC23CC4CC(C2)C(F)(F)C(C4)C3)cc1F
Temperature: 70 °C
Reaction time: 16 h
Yield: 80.5 %

Procedure:
To a solution of (4,4-difluoroadamantan-1-yl)methanol (1.00 g, 4.90 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (1.84 g, 7.40 mmol) in anhydrous dimethylsulfoxide (20 mL) was added cesium carbonate (3.22 g, 9.90 mmol). The mixture was stirred at 70° C. for 16 hours. The mixture was then cooled to ambient temperature, and mixed with water (50 mL). The white solid was filtered and washed with hexanes and dried by air give the title compound as colorless solid (1.70 g, 80%): MS (ES+) m/z 431.1, 433.1 (M+1); 375.0, 377.0 (M−55).
Reaction SMILES: [CH3:1][N:2]([CH2:12][CH2:13][OH:14])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=[O:4].[C:15](Cl)(=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>>[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15](=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=[O:4]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Reactant: Cc1ccc(C(=O)N(C)CCO)cc1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCN(C)C(=O)c1ccc(C)cc1

Procedure:
N-methyl-N-(2-oleoyloxyethyl)-p-toluamide was prepared by the procedure of example 1 from 19 gms. (0.1 mole) of N-methyl-N-(2-hydroxyethyl)-p-toluamide and 30 gms. (0.1 mole) of oleoyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: [N:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=O.[OH-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C>[NH2:1][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=Nc1c(-c2ccccc2)[nH]c2ccccc12
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Nc1c(-c2ccccc2)[nH]c2ccccc12

Procedure:
To a solution of 3-nitroso-2-phenyl indole (28) (25 gm, 0.129 mol) in ethanol (450 ml) was added 2N sodium hydroxide (300 mL, 5.0 eq) followed by sodium dithionite (38 g). The reaction was heated at reflux for 5 h, then filtered. The solid was washed with water and dried under vacuum to provide Compound 29 as a yellow solid. Yield=15 g (72.1%). ES-MS: 209.25 (M++1); NMR (DMSO-d6): 7.0 (m, 1H), 7.1 (m, 1H), 7.22 (m, 1H), 7.32 (m, 2H), 7.40 (m, 1H), 7.48 (m, 2H), 7.60 (m, 1H).
Reaction SMILES: [OH:1][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[CH:3]=1.[CH:25](I)([CH3:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:25]([O:1][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[CH:3]=1)([CH3:27])[CH3:26]
Reactant: Cn1c(=O)n(CCCOC2CCCCO2)c(=O)c2cc(O)cnc21
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Oc1cnc2c(c1)c(=O)n(CCCOC1CCCCO1)c(=O)n2C
Temperature: 80 °C
Yield: 45.4 %

Procedure:
To a solution of 6-hydroxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.1 g, 6.3 mmol) in DMF (20 mL) was added isopropyl iodide (2.14 g, 12.6 mmol) followed by K2CO3 (1.74 g, 12.6 mmol). The reaction was heated at 80° C. for 2 h, cooled to RT, diluted with water (100 mL) then extracted with EA (3×100 mL). The combined organic layers were washed with water (100 mL) then brine (100 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography to give 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (1.08 g, 46% yield over 3 steps) as a solid. 1H NMR (CDCl3) δ: 8.34 (d, J=3.1 Hz, 1H), 7.90 (d, J=3.1 Hz, 1H), 4.69-4.51 (m, 2H), 4.10-4.30 (m, 2H), 3.90-3.78 (m, 2H), 3.69 (s, 3H), 3.51), 3.40-3.70 (m, 2H), 2.01 (dd, J=13.4, 6.7 Hz, 2H), 1.86-1.45 (m, 6H), 1.38 (d, J=6.1 Hz, 6H), 1.26 (t, J=7.1 Hz, 2H). LCMS: [MH+-THP] 294 and TR=1.668 min.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:31]=[CH:30][C:8]([NH:9]/[C:10](=[C:19]2\[C:20](=[O:29])[NH:21][C:22]3[C:27]\2=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)/[C:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH2:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[CH3:3].N1C=CC=CC=1.[C:38]1([S:44](Cl)(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)Cl.[OH-].[Na+]>[CH3:3][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([NH:9]/[C:10](=[C:19]2\[C:20](=[O:29])[NH:21][C:22]3[C:27]\2=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)/[C:11]2[CH:12]=[CH:13][C:14]([CH2:17][NH:18][S:44]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)(=[O:46])=[O:45])=[CH:15][CH:16]=2)=[CH:30][CH:31]=1)[CH3:1]
Reactant: CN(C)Cc1ccc(N/C(=C2\C(=O)Nc3cc(Cl)ccc32)c2ccc(CN)cc2)cc1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: CN(C)Cc1ccc(N/C(=C2\C(=O)Nc3cc(Cl)ccc32)c2ccc(CNS(=O)(=O)c3ccccc3)cc2)cc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
100 mg of 3-Z-[1-(4-dimethylaminomethyl-anilino)-1-(4-aminomethyl-phenyl)-methylene]-6-chloro-2-indolinone (educt 14.0) are dissolved in 5 ml methylene chloride and at 0° C. 5 ml of pyridine and 45 μl of benzenesulphonylchloride are added. The mixture is stirred for 10 minutes at 0° C. and then for 2 hours at ambient temperature. After this time the solvent is eliminated, the residue is suspended in 1N sodium hydroxide solution, suction filtered and washed with a little water. The product is dried at 100° C.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][OH:7].[CH3:8][CH:9]([CH3:25])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:14]=1)=[O:11]>>[OH:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:22]1[CH2:23][CH2:24][CH:19]([C:15]2[CH:14]=[C:13]([NH:12][C:10](=[O:11])[CH:9]([CH3:8])[CH3:25])[CH:18]=[CH:17][CH:16]=2)[CH2:20][CH2:21]1
Reactant: OCCCCCCl
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCO)CC2)c1

Procedure:
Prepared by Procedure G and Scheme B1 using 5-chloro-1-pentanol and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 333.3 (M+H)+.
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[C:18]([CH3:25])[C:17]=1[OH:26].[CH3:27][N:28]([CH3:32])[CH2:29][CH2:30]O>C(OCC)(=O)C>[CH3:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[C:18]([CH3:25])[C:17]=1[O:26][CH2:30][CH2:29][N:28]([CH3:32])[CH3:27]
Reactant: Cc1cc([N+](=O)[O-])cc(C)c1O
Reactant: CN(C)CCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: CCOC(C)=O
Product: Cc1cc([N+](=O)[O-])cc(C)c1OCCN(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
3.4 mL of diisopropyl azodicarboxylate was added to 1.9 g of 2,6-dimethyl-4-nitrophenol and 1.71 mL of 2-dimethylaminoethanol, and stirred at room temperature for 16 hours. The reaction liquid was diluted with ethyl acetate, and the organic layer was extracted with 2 N hydrochloric acid. The aqueous layer was made basic with aqueous 2 N sodium hydroxide solution, and then extracted with ethyl acetate. The organic layer was dried with anhydrous sodium sulfate, and the solvent was evaporated away under reduced pressure to obtain 667 mg of the entitled compound.
Reaction SMILES: [C:1]([C:4]1[N:5]=[CH:6][N:7]2[CH:11]=[C:10]([C:12]3[C@H:13]([CH3:26])[C@@H:14]4[C@@H:21]([C@H:22]([OH:24])[CH3:23])[C:20](=[O:25])[N:15]4[C:16]=3[C:17]([O-:19])=[O:18])[S:9][C:8]=12)(=[O:3])[CH3:2].[Na+].[CH2:28]([O:30][C:31]([O:33][CH:34](I)[CH3:35])=[O:32])[CH3:29].C(OCC)(=O)C>CN(C=O)C>[C:1]([C:4]1[N:5]=[CH:6][N:7]2[CH:11]=[C:10]([C:12]3[C@H:13]([CH3:26])[C@@H:14]4[C@@H:21]([C@H:22]([OH:24])[CH3:23])[C:20](=[O:25])[N:15]4[C:16]=3[C:17]([O:19][CH:28]([O:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH3:29])=[O:18])[S:9][C:8]=12)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ncn2cc(C3=C(C(=O)[O-])N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)sc12
Reactant: CCOC(=O)OC(C)I
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)OC(C)OC(=O)C1=C(c2cn3cnc(C(C)=O)c3s2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Temperature: -10 °C
Reaction time: 2 h
Yield: 64.5 %

Procedure:
Sodium (1S,5R,6S)-2-(7-acetylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (71.9 mg) was dissolved in 2.0 ml of DMF. 1-(Ethoxycarbonyloxy)ethyl iodide (66.3 mg) was added to the solution in an argon atmosphere at −20° C. The mixture was stirred for 2 hr while raising the temperature to −10° C. Ethyl acetate (20 ml) was added to the reaction solution. The mixture was extracted twice, followed by washing twice with 10 ml of semisaturated brine. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under the reduced pressure to a volume of 2 ml. The residue was purified by column chromatography on silica gel (chloroform:methanol=15:1) and Sephadex LH-20 (dichloromethane:methanol=1:1) in that order to give 57.4 mg of the title compound.
Reaction SMILES: [NH2:1][C:2]([CH3:15])([CH3:14])[CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([O:9][CH3:10])=[O:8].[CH2:16]([O:23][C:24]1[CH:25]=[CH:26][C:27]([C@@H:35]([O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:36]Br)=[C:28]2[C:33]=1[NH:32][C:31](=[O:34])[CH:30]=[CH:29]2)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([O:23][C:24]1[CH:25]=[CH:26][C:27]([C@@H:35]([O:38][Si:39]([C:42]([CH3:43])([CH3:45])[CH3:44])([CH3:41])[CH3:40])[CH2:36][NH:1][C:2]([CH3:15])([CH3:14])[CH2:3][C:4]2[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=2)[C:7]([O:9][CH3:10])=[O:8])=[C:28]2[C:33]=1[NH:32][C:31](=[O:34])[CH:30]=[CH:29]2)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1cccc(CC(C)(C)N)c1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Product: COC(=O)c1cccc(CC(C)(C)NC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(OCc3ccccc3)c3[nH]c(=O)ccc23)c1
Temperature: 95 °C
Yield: 49 %

Procedure:
Methyl 3-(2-amino-2-methylpropyl)benzoate (1 g, 4.82 mmol) was added to (R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-one (1.57 g, 3.22 mmol) neat. The resulting mixture was heated to 95° C. for 3 d then cooled. Chromatography (1:3, hexanes/EtOAc) afforded the title compound (970 mg, 49%) as light yellow oil. ES/MS calcd. for C36H47N2O5Si+ 615.3. Found m/z=615.3 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C@H:3]([O:10][C:11](=[O:26])[C:12]1[CH:17]=[CH:16][C:15]([O:18]CC2C=CC=CC=2)=[CH:14][CH:13]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[H][H]>[Pd].C(O)C>[F:1][C:2]([F:27])([F:28])[C@H:3]([O:10][C:11](=[O:26])[C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCC[C@@H](OC(=O)c1ccc(OCc2ccccc2)cc1)C(F)(F)F
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCCCCC[C@@H](OC(=O)c1ccc(O)cc1)C(F)(F)F

Procedure:
The resulting ester compound and 0.13 g of 10% palladium-on-carbon were added to ethanol to conduct debenzylation in a hydrogen atmosphere to obtain 0.39 g of (R)-(+)-4-hydroxybenzoic acid 1-trifluoromethylheptyl ester ##STR7##
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=O)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:22][NH:23][S:24](Cl)(=[O:26])=[O:25].[BH4-].[Na+]>N1C=CC=CC=1>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH:12]2[C:3]3[CH:4]=[CH:5][C:6]4[C:11](=[N:10][CH:9]=[CH:8][CH:7]=4)[C:2]=3[NH:1][S:24](=[O:26])(=[O:25])[N:23]2[CH3:22])=[CH:15][CH:16]=1
Reactant: COc1ccc(C(=O)c2ccc3cccnc3c2N)cc1
Reactant: CNS(=O)(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: c1ccncc1
Product: COc1ccc(C2c3ccc4cccnc4c3NS(=O)(=O)N2C)cc1
Yield: 6.6 %

Procedure:
In a similar fashion using route 27 general procedure 70, (8-amino-quinolin-7-yl)-(4-methoxy-phenyl)-methanone (Intermediate 375) (95 mg, 0.34 mmol), N-methylsulfamoyl chloride (Intermediate 213) (133 mg, 1.02 mmol) and NaBH4 (13 mg, 0.34 mmol) in pyridine (5 ml) gave the title compound (8 mg, 7%) after purification by preparative HPLC (acidic conditions 1).
Reaction SMILES: [CH2:1]([C:3]1[C:7]([CH2:8][C:9]2[CH:17]=[C:16]([CH3:18])[C:15]([O:19][CH3:20])=[C:14]3[C:10]=2[CH2:11][CH2:12][CH2:13]3)=[C:6]([CH2:21][CH3:22])[N:5]([CH2:23][C:24]([NH:26][NH2:27])=[O:25])[N:4]=1)[CH3:2].[C:28](C1NC=CN=1)(C1NC=CN=1)=[O:29].O>O1CCOCC1>[CH2:1]([C:3]1[C:7]([CH2:8][C:9]2[CH:17]=[C:16]([CH3:18])[C:15]([O:19][CH3:20])=[C:14]3[C:10]=2[CH2:11][CH2:12][CH2:13]3)=[C:6]([CH2:21][CH3:22])[N:5]([CH2:23][C:24]2[O:25][C:28](=[O:29])[NH:27][N:26]=2)[N:4]=1)[CH3:2]
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: CCc1nn(CC(=O)NN)c(CC)c1Cc1cc(C)c(OC)c2c1CCC2
Solvent: O
Solvent: C1COCCO1
Product: CCc1nn(Cc2n[nH]c(=O)o2)c(CC)c1Cc1cc(C)c(OC)c2c1CCC2
Temperature: 92.5 °C
Reaction time: 8 h
Yield: 55.4 %

Procedure:
To a stirred solution of [3,5-Diethyl-4-(7-methoxy-6-methyl-indan-4-ylmethyl)-pyrazol-1-yl]-acetic acid hydrazide (1.5 gm, 0.0041 mole) in 1,4-Dioxane (70 ml), Carbonyl-diimidazole (2.0 gm, 0.0121 mole) was added at 20-30° C. The reaction mixture was stirred for 8 hours at 90-95° C. The reaction mixture was cooled and poured into water (200 ml), stirred for 2 hours and then separated solid was filtered. Further the solid was stirred in Diethyl ether (25 ml) and filtered, dried to give 900 mg of desired product as a solid.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]=1[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1[P:25]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=O)(=O)[CH3:2]>O1CCCC1>[CH2:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]=1[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1[P:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH3:2]
Reactant: CC(=O)Nc1ccc2ccccc2c1-c1c(P(=O)(c2ccccc2)c2ccccc2)ccc2ccccc12
Solvent: C1CCOC1
Product: CCNc1ccc2ccccc2c1-c1c(P(c2ccccc2)c2ccccc2)ccc2ccccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.6 %

Procedure:
127 mg (0.25 mmol) of (−)-2-acetylamino-2′-diphenylphosphinyl-1,1′-binaphthyl (the formula (1-2a-1)) was dissolved in 6 ml of tetrahydrofuran under the flow of nitrogen. To the solution, 620 μl (1.24 mmol) of tetrahydrofuran solution (2M) of borane-dimethyl sulfide complex was added at 0° C., followed by the stirring for 18 hours at 88° C. The reaction solution was extracted with 50 ml of ethyl acetate, washed with 10 ml of saturated aqueous solution of ammonium chloride and 10 ml of brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure. To the residue, 6 ml of diethylamine was added and stirred under room temperature for 3 hours. Diethylamine was evaporated under a reduced pressure and the residue was purified using a silica gel column chromatography (eluent: 1:50 mixture of ethyl acetate and hexane) to obtain 91 mg of the titled compound.