Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:13]([Si:21]([CH2:36][CH2:37][CH2:38][Si:39](Cl)(Cl)Cl)([CH2:29][CH2:30][CH2:31][Si:32](Cl)(Cl)Cl)[CH2:22][CH2:23][CH2:24][Si:25](Cl)(Cl)Cl)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].Cl>O1CCCC1>[CH2:13]([Si:21]([CH2:36][CH2:37][CH2:38][SiH2:39][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:7][CH2:8][CH3:9])([CH2:29][CH2:30][CH2:31][SiH2:32][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:4][CH2:5][CH3:6])[CH2:22][CH2:23][CH2:24][SiH2:25][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:1][CH2:2][CH3:3])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCC[Si](CCC[Si](Cl)(Cl)Cl)(CCC[Si](Cl)(Cl)Cl)CCC[Si](Cl)(Cl)Cl
Reactant: CCCCCCCCCC[Mg]Br
Agent: Cl
Solvent: C1CCOC1
Product: CCCCCCCCCCCCC[SiH2]CCC[Si](CCCCCCCC)(CCC[SiH2]CCCCCCCCCCCCC)CCC[SiH2]CCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 15 h
Yield: 81 %

Procedure:
Under a strong nitrogen flow, into a 2 L three-neck round bottom flask equipped with rubber septum, reflux condenser, nitrogen bypass inlet, and magnetic stirring bar was introduced, via a flex-needle, a tetrahydrofuran solution of n-decylmagnesium bromide (114.7 g, 467 mmol). In an inert atmosphere enclosure, into a 50 Ml addition funnel was added n-octyl-tris-[3-(trichlorosilyl)propyl]silane (27.85 g, 41.5 mmol, prepared by the procedure described in Example 1, Step (b)). The addition funnel was attached to the flask containing the n-decylmagnesium bromide solution, and n-octyl-tris-[3-(trichlorosilyl)propyl]silane was added over a period of 40 minutes. The reaction mixture was kept at 50° C. for 15 hours, then allowed to cool to room temperature, and an additional solution of n-decylmagnesium bromide (114.6 g, 467 mmol) in tetrahydrofuran was added into the reaction flask. The reaction mixture was then heated at reflux temperature for 164 hours. After cooling in an ice-water bath, hydrochloric acid (500 Ml, 1.2N) was cautiously added. The reaction mixture separated into two layers on standing. These were separated, and the aqueous layer was extracted with diethyl ether (2×200 Ml). The organic layers were combined, washed with water (200 Ml), and dried over magnesium sulfate, and the solvent removed under reduced pressure. Purification by silica gel column chromatography yielded 54.5 g (81.0%) of n-octyl-tris-[3-(tridecylsilyl)propyl]silane. This tetrasilahydrocarbon had a kinematic viscosity of 89.7 centistokes at 40° C., a kinematic viscosity of 15.4 centistokes at 100° C., and a viscosity index of 182. Onset of volatilization under 0.44 mm Hg pressure, based on thermogravimetric analysis, was at 285° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[C@H:4]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[NH:5][C:6]([C:8]1([NH:13]C(OC(C)(C)C)=O)[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[ClH:30]>ClCCl.C(OCC)(=O)C>[ClH:30].[CH3:1][O:2][C:3](=[O:29])[C@H:4]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=1)[NH:5][C:6]([C:8]1([NH2:13])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7]
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)C1(NC(=O)OC(C)(C)C)CCCC1
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)C1(N)CCCC1

Procedure:
To a solution of N-[[1-[[(1,1-dimethylethoxy)carbonyl]amino]-1-cyclopentyl]-carbonyl]-L-tyrosine methyl ester (3.50 g, 8.6 mmol) in dichloromethane (60 mL) and ethyl acetate (10 mL) is bubbled dry HCl gas for 15 minutes. The solvent is then removed under reduced pressure to give, as a foam, [[1-amino(1-cyclopentyl)]carbonyl]-L-tyrosine methyl ester hydrochloride.
Reaction SMILES: [CH:1]1([CH2:6][CH2:7][N:8]([CH2:22][C:23]2C=CC=CC=2)[CH2:9][CH2:10][CH2:11][NH:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.ClCC(Cl)=[O:32]>>[CH:1]1([CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][N:12]([C:13]3[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=3)[C:23](=[O:32])[CH2:22]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(Cl)CCl
Reactant: O=[N+]([O-])c1ccc(NCCCN(CCC2CCCC2)Cc2ccccc2)cc1
Product: O=C1CN(CCC2CCCC2)CCCN1c1ccc([N+](=O)[O-])cc1

Procedure:
In a manner similar to Preparation 13 react N-[2 (cyclopentyl)ethyl]-N'-(4-nitrophenyl)-N-(phenylmethyl)1,3-propanediamine with chloroacetyl chloride to obtain the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[N:10]=[C:11]=[S:12].[CH3:13][C:14]1[C:19]([CH2:20][NH2:21])=[CH:18][CH:17]=[CH:16][N:15]=1.CO[C@@H]1[C@@H](C(OC)=O)[C@@H]2[C@@H](CN3[C@H](C2)C2NC4C=C(OC)C=CC=4C=2CC3)C[C@H]1OC(C1C=C(OC)C(OC)=C(OC)C=1)=O>C(#N)C>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]([NH:21][CH2:20][C:19]1[C:14]([CH3:13])=[N:15][CH:16]=[CH:17][CH:18]=1)=[S:12]
Reactant: Fc1ccc(N=C=S)c(Cl)c1Cl
Reactant: Cc1ncccc1CN
Agent: COC(=O)[C@H]1[C@H]2C[C@@H]3c4[nH]c5cc(OC)ccc5c4CCN3C[C@H]2C[C@@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)[C@@H]1OC
Solvent: CC#N
Product: Cc1ncccc1CNC(=S)Nc1ccc(F)c(Cl)c1Cl

Procedure:
The title compound was prepared from 2,3-dichloro-4-fluorophenylisothiocyanate and C-(2-methylpyridin-3-yl)methylamine using General Procedure 1. 1H NMR (DMSO-d6, 400 MHz) 2.47 (s, 3H), 4.69 (m, 2H), 7.21 (dd, 1H, J=4.9 Hz, J=7.6 Hz), 7.46 (t, 1H, J=8.9 Hz), 7.54-7.67 (bs, 1H), 7.58 (dd, 1H, J=1.4 Hz, J=7.7 Hz), 8.26-8.42 (bs, 1H), 8.33 (dd, 1H, J=1.7 Hz, J=4.8 Hz), 9.49 (s, 1H); RP-HPLC (Hypersil®-100 C18, 5 μm, 100 Å, 10 cm; 5%-100% acetonitrile-0.1M ammonium acetate over 5 min, 2 mL/min), then 100% acetonitrile isocratic 1 minutes, Rt 3.69 min. (90.8%); MS: M+H-342.
Reaction SMILES: [Cl:1][C:2]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[C:11]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:12]=[C:13]([N+:14]([O-])=[O:15])[C:8]=2[N:7]=[C:6]1[CH3:23]>C(O)C.O.[Fe]>[NH3:5].[OH2:15].[Cl:1][C:2]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[C:11]([N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[CH:12]=[C:13]([NH2:14])[C:8]=2[N:7]=[C:6]1[CH3:23]
Reactant: Cc1nc2c([N+](=O)[O-])cc(N3CCOCC3)cc2n1Cc1cccc(Cl)c1Cl
Agent: [Fe]
Solvent: O
Solvent: CCO
Product: Cc1nc2c(N)cc(N3CCOCC3)cc2n1Cc1cccc(Cl)c1Cl
Product: N
Temperature: 25 °C
Yield: 140.5 %

Procedure:
A mixture of 4-(3-(2,3-dichlorobenzyl)-2-methyl-7-nitro-3H-benzo[d]imidazol-5-yl)morpholine (210 mg), iron powder (56 mg) and FeSO4 (152 mg) in ethanol (25 mL) and H2O (25 mL) was stirred at reflux temperature for 3 h. When TLC showed consumption of all starting material, the mixture was cooled to room temperature and filtered. The filtrate was concentrated in-vacuo and the residue was then purified by silica gel chromatography eluted with MeOH: DCM: NH3.H2O=1:60:0.5% to afford the desired product as a yellow solid (137 mg, 70%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.32 (s, 1H), 2.94 (t, 4H, J=4.8 Hz), 3.68 (t, 4H, J=4.8 Hz), 5.16 (br, s, 2H), 5.40 (s, 2H), 6.09 (d, 1H, J=1.8 Hz), 6.13 (d, 1H, J=1.8 Hz), 6.32 (dd, 1H, J=1.5, 7.5 Hz), 7.25 (t, 1H, J=7.5 Hz), 7.58 (dd, 1H, J=1.5, 7.5 Hz); LC-MS: m/e=391 [M+1]+.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[Cl:11])C=O.C[O-].[Na+].[CH:15](OC)([O:18][CH3:19])[O:16][CH3:17]>CO>[CH3:17][O:16][CH:15]([O:18][CH3:19])[C:8]1[CH:5]=[CH:4][C:3]([Cl:2])=[C:10]([Cl:11])[CH:9]=1
Reactant: COC(OC)OC
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COC(OC)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 89.1 %

Procedure:
Concentrated hydrochloric acid (1.0 ml) was added to a stirred suspension of 3,4-dichlorobenzaldehyde (140 g) in a mixture of trimethyl orthoformate (94 g) and dry methanol (400 ml). After stirring for 24 hours at laboratory temperature (about 25° C.), the reaction solution was adjusted to pH 7-8 by the addition of a solution of sodium methoxide in methanol and concentrated on a rotary evaporator. The residual oil was then dissolved in diethyl ether (600 ml). The ethereal solution was washed with water until the washings were neutral and then dried over anhydrous sodium sulphate, filtered and distilled to give 3,4-dichlorobenzaldehyde dimethyl acetal (157.5 g). b.p. 137°-140° C./25 mm Hg, as a clear mobile oil.
Reaction SMILES: [CH:1]1([N:6]([C:8]([C:10]2[CH:14]=[C:13]([CH3:15])[O:12][C:11]=2[CH3:16])=[O:9])[OH:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].O.S(OC)(O[CH3:24])(=O)=O>ClCCl>[CH3:24][O:7][N:6]([CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)[C:8]([C:10]1[CH:14]=[C:13]([CH3:15])[O:12][C:11]=1[CH3:16])=[O:9]
Reactant: Cc1cc(C(=O)N(O)C2CCCC2)c(C)o1
Reactant: COS(=O)(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CON(C(=O)c1cc(C)oc1C)C1CCCC1
Reaction time: 1 h

Procedure:
14.3 Parts of N-cyclopentyl-2,5-dimethylfuran-3-hydroxamic acid is dissolved in 100 parts of dichloromethane; to this solution there is added a solution of 7.7 parts of sodium hydroxide in 50 parts of water. 16.1 parts of dimethyl sulfate is then dripped into this mixture. After stirring the mixture for 1 hour, the dichloromethane phase is separated, washed with water until neutral, dried over anhydrous sodium sulfate and evaporated. There is obtained 12.1 parts of O-methyl-N-cyclopentyl-2,5-dimethylfuran-3-hydroxamic acid having a boiling point at 0.1 mm Hg of from 103° to 105° C and the refractive index ND25 : 1.5060. ##SPC10##
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8](C(=O)CC)[CH:7]=[CH:6]2.[Br:17][C:18]1[C:27]([O:28][CH3:29])=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][C:22](C(=O)CC)=[CH:23]2.C(Cl)(=O)CC>>[CH3:1][O: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.[Br:17][C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]
Reactant: CCC(=O)c1ccc2cc(OC)ccc2c1
Reactant: CCC(=O)c1ccc2c(Br)c(OC)ccc2c1
Agent: CCC(=O)Cl
Product: COc1ccc2ccccc2c1
Product: COc1ccc2ccccc2c1Br

Procedure:
Compared with the preparation of analogues of the compound II-A, ie 1-(6-methoxy-2-naphthyl)-1-propanone (II, X=H) and 1-(5-bromo-6-methoxy-2-naphthyl)-1-propanone (II, X=Br) by a Friedel-Crafts reaction between propionyl chloride and, respectively, 2-methoxy-naphthalene and 1-bromo-2-methoxy-naphthalene, the following advantages are obtained:
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(O[N:44]1[C:49](=[O:50])[CH2:48][CH2:47][C:45]1=[O:46])=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][N:44]2[C:49](=[O:50])[CH2:48][CH2:47][C:45]2=[O:46])=[O:24])=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)c1ccc(OCCCCCCCCCC(=O)O)cc1
Reactant: CN(C)C(ON1C(=O)CCC1=O)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)c1ccc(OCCCCCCCCCC(=O)ON2C(=O)CCC2=O)cc1
Temperature: 0 °C
Reaction time: 16 h
Yield: 28 %

Procedure:
4-(9-Carboxynonyloxy)benzoic acid tert-butyl ester (779 mg, 2.14 mmol) was dissolved in THF (15 mL), and DIEA (366 μl, 2.14 mmol) was added. The mixture was cooled to 0° C., and placed under nitrogen, and HSTU was added. The mixture was stirred at 0° C. for 30 min and at RT for 16 h. The sample was concentrated under vacuum and AcOEt (40 ml) was added. The mixture was washed with 0.2 N HCl (2×25 ml), dried over MgSO4, and concentrated under vacuum to yield a slightly yellow solid. The solid was recrystallized from AcOEt to yield a white powder (276 mg, 28% yield). The mother liquor was concentrated to yield crystalline residue (430 mg, 43% yield). Data for the white powder:
Reaction SMILES: [C:1]1([CH2:11][NH:12][C:13]([NH:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[N:19][N:20]3C(OC)=O)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO.O>[NH:20]1[C:21]2[C:17](=[C:16]([NH:15][C:13]([NH:12][CH2:11][C:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][CH:2]=3)=[O:14])[CH:24]=[CH:23][CH:22]=2)[CH:18]=[N:19]1
Reactant: COC(=O)n1ncc2c(NC(=O)NCc3cccc4ccccc34)cccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(NCc1cccc2ccccc12)Nc1cccc2[nH]ncc12
Reaction time: 0.5 h

Procedure:
Methyl 4-({[(1-naphthylmethyl)amino]carbonyl}amino)-1H-indazole-1-carboxylate in methanol was treated with 5M sodium hydroxide (8 equivalents) (prepared by dissolution of 1 gram of sodium hydroxide in 20 μL of methanol). After stirring for 30 minutes, the mixture was diluted with water (10 mL) and filtered. The filter cake was washed with water (10 mL), water:methanol (1:1), and dried under reduced pressure to provide the title compound. MS (M+H)+ 317.
Reaction SMILES: [CH3:1][O-:2].[Na+].[Cl:4][C:5]1[C:6]([N:11]2[CH2:20][CH2:19][C:18]3[C:17]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)=[N:16][C:15](S(C)(=O)=O)=[N:14][C:13]=3[CH2:12]2)=[N:7][CH:8]=[CH:9][CH:10]=1>CO>[Cl:4][C:5]1[C:6]([N:11]2[CH2:20][CH2:19][C:18]3[C:17]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)=[N:16][C:15]([O:2][CH3:1])=[N:14][C:13]=3[CH2:12]2)=[N:7][CH:8]=[CH:9][CH:10]=1
Reactant: CS(=O)(=O)c1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ncccc1Cl)C2
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1nc2c(c(Nc3ccc(C(F)(F)F)cc3)n1)CCN(c1ncccc1Cl)C2
Temperature: 60 °C
Reaction time: 8 h
Yield: 80.3 %

Procedure:
Sodium methoxide (16 mg, 0.3 mmol) was added to a suspension of 7-(3-chloropyridin-2-yl)-N-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-2-(methylsulfonyl)pyrido[3,4-d]pyrimidin-4-amine from Example 25 (100 mg, 0.2 mmol) in methanol (5 mL, anhydrous) and stirred at 60° C. overnight. Solvent was removed in vacuo, residue was dissolved in ethyl acetate and washed with water and brine and dried over sodium sulfate. After concentration, solid residue was triturated by diethyl ether to yield the product as a white powder (70 mg).
Reaction SMILES: [SiH3]O[SiH3].O.O.O.[F-:7].C([N+]([CH2:21][CH2:22][CH2:23][CH3:24])(CCCC)CCCC)CCC.[O:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>>[F:7][C:21](=[CH:22][CH2:23][CH:24]=[CH:21][CH2:22][CH2:23][CH2:24][CH2:21][CH:22]=[CH:23][CH2:24][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:29][CH2:28][CH2:27][CH2:26][OH:25]
Reactant: [F-]
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Reactant: C1CCOC1
Agent: [SiH3]O[SiH3]
Solvent: O
Product: CCCCCC=CCCCCC=CCC=C(F)CCCCO
Temperature: 25 °C
Reaction time: 2 h
Yield: 88 %

Procedure:
To a solution of the silylether prepared in 1N (237 mg, 0.43 mmole) in tetrahydrofuran (5 ml) was added tetra-n-butylammonium fluoride trihydrate (205 mg, 0.65 mmole). The mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride, washed with water and dried over sodium sulfate. Filtration and concentration under reduced pressure afforded an oil. Flash chromatography on silicagel and elution with a 15:95 mixture of ethyl-acetate and benzene afforded the expected alcohol as an oil (119 mg, 88%). NMR (H1, CDCl3, 360 MHz) characteristic peaks: 2.32 (dm, JHF =21.6 Hz, 2), 2.72 (t, JHH =7 HZ, 2), 3.73 (m, 2), 5.09 (dt, JHF =21.6 Hz, JHH =8 Hz, 1), 5.39 (m, 4).
Reaction SMILES: [Cl-:1].[NH4+].[P:3]([Cl:8])([Cl:7])([Cl:6])([Cl:5])[Cl:4]>>[P:3]([Cl:8])([Cl:7])([Cl:6])([Cl:5])[Cl:4].[P:3]([Cl:6])([Cl:5])[Cl:4].[Cl:1][Cl:4]
Reactant: [Cl-]
Agent: ClP(Cl)(Cl)(Cl)Cl
Agent: [NH4+]
Product: ClCl
Product: ClP(Cl)Cl

Procedure:
This reaction of ammonium chloride and phosphorus pentachloride may be carried out, while producing phosphorus pentachloride from phosphorus trichloride and chlorine. In this case, phosphorus trichloride is employed as the starting material instead of phosphorus pentachloride. Ammonium chloride, phosphorus trichloride and a catalyst are dispersed in an organic solvent inert to chlorine, and then the temperature is raised to 100° to 200° C. and chlorine gas is supplied into the dispersion to start the reaction. The reaction is carried out under reflux with stirring. During the reaction, an approximately equimolar amount of chlorine gas with phosphorus trichloride is supplied at a rate of 0.1 to 1.5 g./minute per mole of phosphorus trichloride to produce phosphorus pentachloride. The resulting phosphorus pentachloride reacts with ammonium chloride to produce the phosphonitrilic chloride oligomers. After the completion of the supply of chlorine gas, the reaction is further continued at a temperature of 100° to 200° C. for 0.5 to 2 hours under reflux with stirring to complete the reaction.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH2:10])=[NH:9])=[N:6][CH:7]=1.[CH3:11][CH:12]([C:18](=O)[CH3:19])[C:13](OCC)=[O:14].C(=O)([O-])[O-].[Na+].[Na+]>O.C(O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:10]=[C:13]([OH:14])[C:12]([CH3:11])=[C:18]([CH3:19])[N:9]=2)=[N:6][CH:7]=1
Reactant: N=C(N)c1ccc(N)cn1
Reactant: CCOC(=O)C(C)C(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1nc(-c2ccc(N)cn2)nc(O)c1C
Reaction time: 24 h

Procedure:
To a solution of compound of example 12 (0.2 g, 1.47 mmol) in water (5 mL) and ethanol (2.5 mL) was added ethyl 2-methyl-3-oxobutanoate (0.339 g, 2.35 mmol) and sodium carbonate (0.280 g, 2.64 mmol) at room temperature and the reaction mixture was stirred for 24 hours. Ethanol was removed under reduced pressure, and the reaction mixture was diluted with water and extracted with ethyl acetate (3×20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by column chromatography using silica gel and 1% methanol in chloroform as an eluent to obtain the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:13][C@H:14]([C:16]([NH:18][CH:19]1[N:25]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:23]2[CH:33]=[CH:34][CH:35]=[CH:36][C:22]=2[N:21]([CH3:37])[C:20]1=[O:38])=[O:17])[CH3:15]>>[F:8][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([NH:13][C@H:14]([C:16]([NH:18][CH:19]2[N:25]=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[C:23]3[CH:33]=[CH:34][CH:35]=[CH:36][C:22]=3[N:21]([CH3:37])[C:20]2=[O:38])=[O:17])[CH3:15])=[O:12])[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: O=C(O)Cc1cc(F)cc(F)c1
Reactant: C[C@H](N)C(=O)NC1N=C(c2ccc(F)cc2)c2ccccc2N(C)C1=O
Product: C[C@H](NC(=O)Cc1cc(F)cc(F)c1)C(=O)NC1N=C(c2ccc(F)cc2)c2ccccc2N(C)C1=O

Procedure:
Following General Procedure D above using 3,5-difluorophenylacetic acid (Oakwood Products, Inc.) and 3-(L-alaninyl)-amino-2,3-dihydro-1-methyl-5-(4-fluorophenyl)-1H-1,4-benzodiazepin-2-one (Example 8-K), the title compound was prepared as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:16][Br:17])[CH2:12][CH2:11][CH:10]([CH2:13]CC)[O:9]2)=[CH:4][CH:3]=1.Cl[C:19]1C=CC(C(CCC(O)(C)C)=C)=CC=1.BrBr.N1C=CC=CC=1>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:16][Br:17])[CH2:12][CH2:11][C:10]([CH3:13])([CH3:19])[O:9]2)=[CH:6][CH:7]=1
Reactant: CCCC1CCC(CBr)(c2ccc(Cl)cc2)O1
Reactant: C=C(CCC(C)(C)O)c1ccc(Cl)cc1
Agent: BrBr
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC1(C)CCC(CBr)(c2ccc(Cl)cc2)O1

Procedure:
By the cyclisation procedure described for the preparation of 2-(4-chlorophenyl)-2-bromomethyl-5-prop-1-yltetrahydrofuran (see Example 1), 2-(4-chlorophenyl)-5-hydroxy-5-methylhex-1-ene (5.3 g), bromine (3.8 g), and pyridine (1.9 g), in dichloromethane (60 ml), gave 2-(4-chlorophenyl)-2-bromomethyl-5,5-dimethyltetrahydrofuran (7.6 g) as a red oil, 1H nmr (CDCl3): δ1.2 (3H, singlet) and 1.4 (3H, singlet), 2×CH3, 3.5 (2H, singlet, CH2Br).
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.[CH3:42][N:43]([CH3:50])[CH2:44][C:45]([CH3:49])([CH3:48])[CH2:46][NH2:47]>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:47][CH2:46][C:45]([CH3:49])([CH3:48])[CH2:44][N:43]([CH3:50])[CH3:42])=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Reactant: CN(C)CC(C)(C)CN
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1cc(C(=O)NCC(C)(C)CN(C)C)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
To a mixture of 0.10 g (0.22 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-100), 0.12 mL (0.66 mmole) of ethyldiisopropyl amine and 0.039 mL (0.25 mmole) of N,N,-2,2-tetramethyl-propane-1,3-diamine in 2.0 mL of dimethylformamide was added 0.11 g (0.25 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) gave 0.080 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-2,2-dimethyl-propyl)-3-methoxy-benzamide (I-60) as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([OH:20])[CH:18]=3)[C:13]([C:21]#[N:22])=[CH:12]2)=[CH:7][C:6]=1[O:23][CH2:24][O:25][CH3:26])[CH3:2].[CH2:28]([O:35][C:36](=[O:41])[NH:37][CH2:38][CH2:39]Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:39][CH2:38][NH:37][C:36]([O:35][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:41])[CH:18]=3)[C:13]([C:21]#[N:22])=[CH:12]2)=[CH:7][C:6]=1[O:23][CH2:24][O:25][CH3:26])[CH3:2]
Reactant: O=C(NCCBr)OCc1ccccc1
Reactant: CCOC(=O)c1ccc(-n2cc(C#N)c3ccc(O)cc32)cc1OCOC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(-n2cc(C#N)c3ccc(OCCNC(=O)OCc4ccccc4)cc32)cc1OCOC
Temperature: 50 °C
Reaction time: 8 h
Yield: 72.9 %

Procedure:
To a solution of 4-(3-cyano-6-hydroxyindol-1-yl)-2-methoxymethoxybenzoic acid ethyl ester (0.37 g) in N,N-dimethylformamide (10 mL) were added (2-bromoethyl)carbamic acid benzyl ester (0.39 g) and potassium carbonate (0.28 g), and this mixture was stirred at 50° C. overnight. This reaction mixture was poured into water, and the precipitated solid was collected by filtration. This solid was washed with methanol, and dried to give the title compound (0.40 g).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].[CH2:11]([OH:13])C>>[O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:13])[OH:10])[OH:8])[OH:6])[OH:4]
Reactant: CCO
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
The results presented in FIG. 2 show that in contrast to the control strain containing the shuttle vector alone (CP4[pZB 186]), the recombinant containing the added xylose isomerase, xylulokinase, transaldolase and transketolase genes demonstrated growth and ethanol production from xylose as a carbon source. The recombinant strain produces ethanol from glucose as efficiently as the control strain at 94% of theoretical yield. The recombinant strain additionally produces ethanol from xylose at 84% of theoretical yield in 79 hours. Furthermore, in the combined presence of glucose and xylose, the recombinant strain ferments both sugars simultaneously to ethanol at 88% of theoretical yield within 48 hours, thus providing the foundation for advanced process designs with cofermentation of mixed-sugar feedstocks.