Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[C:12]([C:14]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[CH:19][C:15]=1[C:16](Cl)=[O:17])#[N:13].O>CN(C)C=O>[C:12]([C:14]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[CH:19][C:15]=1[C:16]([N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6])=[O:17])#[N:13]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: N#Cc1ccc(Oc2ccc(Cl)cc2Cl)cc1C(=O)Cl
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1ccc(Oc2ccc(Cl)cc2Cl)cc1C(=O)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The N-potassium salt of phthalimide (0.025 mole) dissolved in dimethylformamide (50 ml) and 2-cyano-5-(2,4-dichlorophenoxy)benzoyl chloride (0.025 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is stirred at room temperature for a period of about 8 hours. After this time the mixture is poured into water (150 ml) and is extracted twice with toluene. The toluene extracts are combined and stripped of solvent leaving a solid residue. This residue is recrystallized to yield the desired product N-[2-cyano-5-(2,4-dichlorophenoxy)benzoyl]phthalimide.
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]2[CH:14]=[N:15][N:16]=[C:12]2[C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[C:10]([C:27]2[CH:32]=[CH:31][N:30]=[C:29](Cl)[CH:28]=2)[N:9]=1.C(OC(N1CC=C(C2N3C=NN=C3C(C3C=CC=C(C(F)(F)F)C=3)=C(C3C=CN=C([NH:72][C@H:73]([C:75]4[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=4)[CH3:74])C=3)N=2)CC1)=O)(C)(C)C>>[OH:1][CH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]2[CH:14]=[N:15][N:16]=[C:12]2[C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[C:10]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:72][C@H:73]([C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)[CH3:74])[CH:28]=2)[N:9]=1
Reactant: C[C@H](Nc1cc(-c2nc(C3=CCN(C(=O)OC(C)(C)C)CC3)n3cnnc3c2-c2cccc(C(F)(F)F)c2)ccn1)c1ccccc1
Reactant: OC[C@H]1CCCN1c1nc(-c2ccnc(Cl)c2)c(-c2cccc(C(F)(F)F)c2)c2nncn12
Product: C[C@H](Nc1cc(-c2nc(N3CCC[C@@H]3CO)n3cnnc3c2-c2cccc(C(F)(F)F)c2)ccn1)c1ccccc1

Procedure:
The title compound was synthesized from 5-(2(R)-(hydroxymethyl)-pyrrolidin-1-yl)-7-(2-chloro-4-pyridyl)-8-(3-(trifluoromethyl)phenyl)-1,2,4-triazolo[4,3-c]pyrimidine in the same manner as 5-(1-(t-butoxycarbonyl)-1,2,3,6-tetrahydropyrid-4-yl)-7-(2-(1(S)-phenylethyl)amino-4-pyridyl)-8-(3-(trifluoromethyl)phenyl)-1,2,4-triazolo[4,3-c]pyrimidine; MS (m/z) 560.4 (M+H)+; C30H28F3N7O requir. 559.59.
Reaction SMILES: [Br:1][C:2]1[C:14]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][S:20][C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[CH:13][C:5]2[C:6]([CH3:12])([CH3:11])[O:7][C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1.[OH:28]O>>[Br:1][C:2]1[C:14]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][S:20]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[O:28])=[CH:13][C:5]2[C:6]([CH3:12])([CH3:11])[O:7][C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1
Reactant: Cc1ccc(SCCCCOc2cc3c(cc2Br)NC(=O)OC3(C)C)cc1
Reactant: OO
Product: Cc1ccc(S(=O)CCCCOc2cc3c(cc2Br)NC(=O)OC3(C)C)cc1

Procedure:
Prepared analogously to Example 2 from 7-bromo-6-[4-(4-methyl-phenylmercapto)-butoxy]-4,4-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([CH3:26])[C:8]([C:10]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][N:13]=[C:12](S(C)(=O)=O)[N:11]=1)=[O:9].O1[CH2:41][CH2:40]OCC1>>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([CH3:26])[C:8]([C:10]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][N:13]=[C:12]([N:11]2[CH2:41][CH2:40][N:7]([CH3:6])[CH2:8][CH2:10]2)[N:11]=1)=[O:9]
Reactant: CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)c1nc(S(C)(=O)=O)ncc1-c1ccccc1
Reactant: C1COCCO1
Product: CN1CCN(c2ncc(-c3ccccc3)c(C(=O)N(C)Cc3cc(C(F)(F)F)cc(C(F)(F)F)c3)n2)CC1
Reaction time: 16 h
Yield: 96.2 %

Procedure:
To a solution of 0.3 g (0.58 mmol) 2-methanesulfonyl-5-phenyl-pyrimidine-4-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide in 10 ml dioxan 0.16 ml (1.45 mmol) 1-methyl-piperazine was added. The reaction mixture was stirred for 16 hrs. After evaporation of the solvent, the residue was distributed between 50 ml CH2Cl2 and 50 ml H2O. The aqueous layer was extracted with 50 ml CH2Cl2, the combined organic layers dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (SiO2, CH2Cl2/MeOH/NH4OH 140:10:1) to give 0.15 g (48%) 2-(4-methyl-piperazin-1-yl)-5-phenyl-pyrimidine-4-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide as a off-white solid, m.p. 162.0-162.8°.
Reaction SMILES: BrC1C=C(NC(=O)C)C=C(C(C2C=NC=CC=2)=O)C=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:28]2[CH:29]=[C:30]([NH:53][C:54](=[O:56])[CH3:55])[CH:31]=[C:32]([C:34]3[CH:42]=[CH:41][CH:40]=[C:39]4[C:35]=3[CH:36]=[CH:37][N:38]4[Si](C(C)C)(C(C)C)C(C)C)[CH:33]=2)=[O:27])[CH:21]=1>>[NH:38]1[C:39]2[C:35](=[C:34]([C:32]3[CH:31]=[C:30]([NH:53][C:54](=[O:56])[CH3:55])[CH:29]=[C:28]([C:26]([C:22]4[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=4)=[O:27])[CH:33]=3)[CH:42]=[CH:41][CH:40]=2)[CH:36]=[CH:37]1
Reactant: CC(=O)Nc1cc(C(=O)c2cccnc2)cc(-c2cccc3c2ccn3[Si](C(C)C)(C(C)C)C(C)C)c1
Agent: CC(=O)Nc1cc(Br)cc(C(=O)c2cccnc2)c1
Product: CC(=O)Nc1cc(C(=O)c2cccnc2)cc(-c2cccc3[nH]ccc23)c1

Procedure:
N-[3-bromo-5-(pyridine-3-carbonyl)-phenyl]-acetamide was converted to N-[3-(pyridine-3-carbonyl)-5-(1-triisopropylsilanyl-1H-indol-4-yl)-phenyl]-acetamide, and the triisopropylsilyl group was removed with tetra n-butylammonium fluoride to give N-[3-(1H-indol-4-yl)-5-(pyridine-3-carbonyl)-phenyl]-acetamide as described in Example 35. 1H NMR (400 MHz, methanol-d4): δ 10.61 (s, 1H), 8.94 (s, 1H), 8.70 (s, 1H), 8.13-8.19 (m, 2H), 7.99 (s, 1H), 7.74 (s, 1H), 7.49 (s, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.25 (s, 1H), 7.13 (t, J=7.7 Hz, 1H), 7.06 (d, J=7.0 Hz, 1H), 6.62 (s, 1H), 2.12 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]3[CH2:13][CH2:14][N:15]=[C:16]([CH3:17])[C:11]3=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+].[C:20]([OH:27])(=[O:26])/[CH:21]=[CH:22]/[C:23]([OH:25])=[O:24]>CO.O.C(O)C>[C:20]([OH:27])(=[O:26])/[CH:21]=[CH:22]/[C:23]([OH:25])=[O:24].[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]3[CH2:13][CH2:14][NH:15][CH:16]([CH3:17])[C:11]3=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC1=NCCn2c1ccc2-c1cccc(Cl)c1
Agent: O=C(O)/C=C/C(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: CO
Product: CC1NCCn2c(-c3cccc(Cl)c3)ccc21
Yield: 57 %

Procedure:
6-(m-Chlorophenyl)-3,4-dihydro-1-methylpyrrolo[1,2-a]pyrazine (2.0 g) was dissolved in a mixture of 100 ml of methanol and 10 ml of water under argon. The solution was treated portionwise with 0.9 g of sodium borohydride while stirring and stirred at room temperature overnight. Thereafter, the methanol was removed in a vacuum, the residue was taken up in 150 ml of methylene chloride and washed with 50 ml of 10% ammonia solution. The phases were separated and the aqueous phase was extracted twice with 70 ml of methylene chloride each time. The organic phases were combined, dried with MgSO4 and freed from solvent. The crude product, 2.0 g of yellow oil, was dissolved in a 20-fold amount of ethanol and treated with 1.1 equivalents of a saturated solution of fumaric acid in ethanol. The solution was concentrated to 10 ml and boiled briefly with 100 ml of ethyl acetate. There were obtained 1.7 g (57%) of 6-(m-chlorophenyl)-1,2,3,4-tetrahydro-1 -methylpyrrolo[1,2-a]pyrazine fumarate (1:1); m.pt.: 165°-167° C. (dec.).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7].CN(C)C(=N)N(C)C.[C:17]([O:21][C:22](N=[N+]=[N-])=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C)C=O>[C:17]([O:21][C:22]([CH:5]([CH2:4][CH2:3][CH2:2][NH2:1])[C:6]([OH:8])=[O:7])=[O:23])([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)N=[N+]=[N-]
Reactant: NCCCCC(=O)O
Agent: CN(C)C(=N)N(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)C(CCCN)C(=O)O
Yield: 70 %

Procedure:
5-Amino pentanoic acid (0.585 g, 5 m mol) was stirred for two days in dimethylformamide (5 ml) containing tetramethylguanidine (1.14 g, 10 m mol) and tert.butoxycarbonylazide (1.1 g, 7.5 m mol). The solution was evaporated and the residue partitioned between ethyl acetate (20 ml) and 10% citric acid solution (20 ml). The organic layer was washed with 10% citric acid (2×15 ml), water (3×15 ml) and brine 1×15 ml). Each aqueous wash was back extracted with ethyl acetate (20 ml). The combined organic layers were dried over anhydrous magnesium sulphate and evaporated to give an oil which slowly crystallised. Recrystallisation from diisopropyl ether/petrol gave 0.745 g (70% yield), mp. 47.5°-48.5° C., Rf silica gel 0.40 (benzene:dioxan:acetic acid 95:75:4).
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:35])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](OC2C=CC([N+]([O-])=O)=CC=2)=[O:24])=[CH:18][CH:17]=1)[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:2]=[CH2:3].[NH2:36][CH2:37][CH2:38][C@H:39]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:40]([OH:42])=[O:41].C(N(CC)C(C)C)(C)C>ClCCl>[CH2:1]([O:4][C:5](=[O:35])[C@@H:6]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([NH:36][CH2:37][CH2:38][C@H:39]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:40]([OH:42])=[O:41])=[O:24])=[CH:18][CH:17]=1)[CH:2]=[CH2:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCN)C(=O)O
Reactant: C=CCOC(=O)[C@H](Cc1ccc(OC(=O)Oc2ccc([N+](=O)[O-])cc2)cc1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCOC(=O)[C@H](Cc1ccc(OC(=O)NCC[C@H](NC(=O)OC(C)(C)C)C(=O)O)cc1)NC(=O)OC(C)(C)C
Temperature: 75 °C

Procedure:
4.0 g (8.22 mmol) of the compound from example 1A was dissolved in 60 ml dichloromethane. 1.795 (8.22 mmol) (2S)-4-Amino-2-[(tert-butoxycarbonyl)amino]butanoic acid and 1.43 ml (8.22 mmol) N,N-diisopropylethylamine were added. The reaction mixture was split into 3 portions. The portions were heated for 30 min in a sealed tube at 75° C. in a microwave synthesizer. From the combined reaction mixture the solvent was removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.). The raw product was dissolved in dichloromethane and chromatographed over approx. 600 ml silica gel. Solvents used were dichloromethane/ethyl acetate 4/1, dichloromethane/ethyl acetate 1/1, dichloromethane/methanol 4/1 and dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 4.02 g (6.54 mmol, 80% of theory) of the desired product.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[C:5]([O:13][CH3:14])[CH:4]=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=[O:20].C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O>>[Br:15][C:16]1[CH:17]=[C:18]([C:19]([C:3]2[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[C:5]([O:13][CH3:14])[CH:4]=2)=[O:20])[CH:21]=[CH:22][CH:23]=1
Reactant: O=Cc1cccc(Br)c1
Reactant: COc1cc(Br)cc(OC)c1OC
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: [Mg]
Agent: c1cc[nH+]cc1
Product: COc1cc(C(=O)c2cccc(Br)c2)cc(OC)c1OC

Procedure:
First, magnesium was added to 1-bromo-3,4,5-trimethoxybenzene as a starting material, as shown in Reaction 6, and then 3-bromobenzaldehyde was added thereto to obtain a compound. Thus obtained compound was oxidized using PDC to obtain a Compound 21 derivative [(3-bromophenyl)(3,4,5-trimethoxyphenyl)methanone]. Thus obtained compound and thiophen-3-boronic acid were subjected to the Suzuki reaction, in the same manner as in the synthesis of Compound 457, to obtain Compound 568.
Reaction SMILES: [C:1](C(CC)C(OCC)=O)#N.CNC(N)=O.[NH2:16][C:17]1[N:22]([CH2:23]C)[C:21](=[O:25])[NH:20][C:19](=[O:26])[C:18]=1[CH3:27]>>[NH2:16][C:17]1[N:22]([CH3:23])[C:21](=[O:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:27][CH3:1]
Reactant: CCOC(=O)C(C#N)CC
Reactant: CCn1c(N)c(C)c(=O)[nH]c1=O
Agent: CNC(N)=O
Product: CCc1c(N)n(C)c(=O)[nH]c1=O

Procedure:
Ethyl 2-cyanobutanoate was reacted with 1-methylurea according to the method described for synthesis of C9 in Example 5. The product was obtained as a white solid. Yield: 5.95 g, 35.2 mmol, 66%. 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 6.41 (s, 2H), 3.22 (s, 3H), 2.22 (q, J=7.3 Hz, 2H), 0.87 (t, J=7.3 Hz, 3H).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:13]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:12](=[O:22])[N:7]2[C:8]=1[C:9]([O-:11])=[O:10].[K+].ClC(Cl)(Cl)C[O:27][C:28]([N:30]=C=O)=O>>[C:28]([O:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:13]([NH:14][C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[C:12](=[O:22])[N:7]2[C:8]=1[C:9]([OH:11])=[O:10])(=[O:27])[NH2:30]
Reactant: O=C=NC(=O)OCC(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)NC1C(=O)N2C(C(=O)[O-])=C(CO)CS[C@H]12
Agent: [K+]
Product: CC(C)(C)OC(=O)NC1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12

Procedure:
5 g. of potassium 3-hydroxymethyl-7-[N-(t-butoxycarbonyl)amino]-3-cephem-4-carboxylate is reacted with 2,2,2-trichloroethoxycarbonyl isocyanate and the resulting product is deblocked following the procedures described in Example 5 to afford 3-carbamoyloxymethyl-7-[N-(t-butoxycarbonyl)amino]-3-cephem-4-carboxylic acid.
Reaction SMILES: C1(C=O)CC1.[CH:6]1([CH:9]=[N:10][S:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH2:8][CH2:7]1>C(Cl)Cl.[O-]S([O-])(=O)=O.[Cu+2]>[CH:6]1([CH:9]=[N:10][S@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH2:7][CH2:8]1
Reactant: CC(C)(C)S(=O)N=CC1CC1
Agent: [Cu+2]
Agent: O=CC1CC1
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Product: CC(C)(C)[S@](=O)N=CC1CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
The title compound was prepared according to a general procedure described by G. Liu, D. A. Cogan, T. D. Owens, T. P. Tang, and J. A. Ellman J. Org. Chem. 1999, 64, 1278: A mixture of cyclopropanecarboxaldehyde (35.0 g, 0.5 mol), 2-methyl-2-propanesulfinic acid 1-cyclopropyl-methylideneamide (30 g, 0.25 mol) and anhydrous CuSO4 (120 g, 0.75 mol) in CH2Cl2 (1500 mL) was stirred at room temperature overnight. The reaction mixture was filtered and evaporated to give the title compound (39 g, yield 95%), which was used in the next step without further purification.
Reaction SMILES: [CH3:1][Mg]Br.[Br:4][C:5]1[CH:6]=[C:7]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[CH:8]=[O:9]>C1COCC1>[Br:4][C:5]1[CH:6]=[C:7]([CH:8]([OH:9])[CH3:1])[CH:10]=[C:11]([C:13]([F:14])([F:15])[F:16])[CH:12]=1
Reactant: C[Mg]Br
Reactant: O=Cc1cc(Br)cc(C(F)(F)F)c1
Solvent: C1CCOC1
Product: CC(O)c1cc(Br)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91 %

Procedure:
To a stirred solution at −10° C. of methyl magnesium bromide (38.00 mL, 3.0 M in ethyl ether, 114.0 mmol) in THF (200.0 mL) was added dropwise a solution of 3-bromo-5-(trifluoromethyl)benzaldehyde (Reference Example 39, 22.01 g, 86.98 mmol) in THF (100 mL) and after the addition was complete, the reaction mixture was held at −10° C. for 2 h. After this time, the reaction was quenched with saturated ammonium hydrochloride (300.0 mL) and warmed to room temperature. The reaction mixture was diluted with ethyl acetate, washed with water, and saturated sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure to provide 1-(3-bromo-5-(trifluoromethyl)phenyl)ethanol (21.30 g, 91%) as a pale yellow oil.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:16]2[C:11](=[CH:12][N:13]=[C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:15]=2)[CH:10]=[CH:9][N:8]=1)(=O)=O.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=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>[CH2:18]([O:17][C:14]1[CH:15]=[C:16]2[C:11]([CH:10]=[CH:9][N:8]=[C:7]2[C:31]2[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=2)=[CH:12][N:13]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=S(=O)(Oc1nccc2cnc(OCc3ccccc3)cc12)C(F)(F)F
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)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: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: Cn1cc(-c2nccc3cnc(OCc4ccccc4)cc23)cn1
Temperature: 100 °C
Yield: 86.4 %

Procedure:
To a suspension of 7-(benzyloxy)-2,6-naphthyridin-1-yl trifluoromethanesulfonate (Preparation 87, 350 mg, 0.911 mmol) in 1,4-dioxane (6 mL) and water (3 mL) was added 1-Methylpyrazole-4-boronic acid pinacol ester (379 mg, 1.821 mmol), cesium carbonate (460 mg, 1.412 mmol) and Pd(PPh3)4 (220 mg, 0.190 mmol). The reaction mixture was heated to 100° C. for 30 minutes under microwave conditions. The reaction mixture was diluted with EtOAc (25 mL) and water (25 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-15% MeOH in DCM followed by a second chromatography eluting with 0-10% MeOH in DCM to give the title compound (249 mg, 86%).
Reaction SMILES: [C:1](=[O:38])([O:16][CH2:17]/[C:18](/[C:28]1[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1)=[C:19](/[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)\[CH2:20][OH:21])[O:2][CH2:3][CH2:4][CH2:5][CH:6]([O:12][N+:13]([O-:15])=[O:14])[CH2:7][O:8][N+:9]([O-:11])=[O:10].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=[O:41].O>ClCCl>[N+:13]([O:12][CH:6]([CH2:7][O:8][N+:9]([O-:11])=[O:10])[CH2:5][CH2:4][CH2:3][O:2][C:1]([O:16][CH2:17]/[C:18](/[C:28]1[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:30][CH:29]=1)=[C:19](/[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)\[C:20]([OH:41])=[O:21])=[O:38])([O-:15])=[O:14]
Reactant: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Reactant: CS(=O)(=O)c1ccc(/C(COC(=O)OCCCC(CO[N+](=O)[O-])O[N+](=O)[O-])=C(/CO)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Product: CS(=O)(=O)c1ccc(/C(COC(=O)OCCCC(CO[N+](=O)[O-])O[N+](=O)[O-])=C(/C(=O)O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 56.4 %

Procedure:
To a solution of 4.5 g of 4,5-bis(nitrooxy)pentyl (2Z)-4-hydroxy-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-yl carbonate in 50 mL of dichloromethane, 4.13 g of Dess-Martin reagent was added and the resulted mixture was stirred at 25° C. for 45 min. Then 250 uL of water was added and the mixture was stirred at RT for 15 min. Then the mixture was filtered through a pad of silica gel and evaporated. The crude was dissolved in a mixture of THF and t-BuOH (25 mL/25 mL). To this solution was added 6.8 mL of 2-methyl-2-butene followed by the addition of 20 mL of phosphoric acid (1.2M soln) and 20 mL of NaClO2 (1M soln). The resulted mixture was stirred at RT for 30 min. The organic phase was separated and the aqueous phase was extracted with EtOAc. The organic phases were combined, dried over Na2SO4, filtered, and then evaporated. The crude was purified by flash chromatography to afford 2.6 g of the titled compound as white solid. 1H NMR (acetone-d6, 500 MHz): δ 7.77 (d, 2H), 7.44 (d, 2H), 7.17 (s, 3H), 7.12 (t, 2H), 5.51 (s, 1H), 5.35 (s, 2H), 5.00 (dd, 1H), 4.72 (dd, 1H), 4.13-4.10 (m, 2H), 3.06 (s, 3H), 1.87-1.80 (m, 4H).
Reaction SMILES: [CH2:1]([PH2:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH:10]([CH:12]=[O:13])=[O:11]>>[CH2:1]([P:9]1[CH:10]([OH:11])[CH:12]([OH:13])[P:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:10]([OH:11])[CH:12]1[OH:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCP
Reactant: O=CC=O
Product: CCCCCCCCP1C(O)C(O)P(CCCCCCCC)C(O)C1O

Procedure:
Following the procedure of Example 1, 200 parts of mono-n-octylphosphine is reacted with 194 parts of glyoxal to give 1,4-di-n-octyl-2,3,5,6-tetrahydroxy-1,4-diphosphorinane, a waxy solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:21]=[C:20]([Cl:22])[N:19]=[C:18]([NH2:23])[N:17]=2)=[C:11]([N+:24]([O-])=O)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+].O1CCCC1.O>CO.[Fe]>[NH2:24][C:11]1[CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:14]=[CH:13][C:12]=1[S:15][C:16]1[CH:21]=[C:20]([Cl:22])[N:19]=[C:18]([NH2:23])[N:17]=1
Reactant: Nc1nc(Cl)cc(Sc2ccc(OCc3ccccc3)cc2[N+](=O)[O-])n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Nc1nc(Cl)cc(Sc2ccc(OCc3ccccc3)cc2N)n1
Yield: 43.4 %

Procedure:
A solution of the product from Example 217C (0.1 g, 0.257 mmol), iron powder (0.058 g, 1.03 mmol) and ammonium chloride (0.017 g, 0.310 mmol) in a methanol (5 mL), tetrahydrofuran (5 mL), and water (2 mL) solution was heated to reflux for 1.5 hours. The resultant mixture was diluted with methanol (50 mL) and filtered through a pad of celite. The filtrate was concentrated under vacuum to a volume of 10 mL, the solution diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined extracts were washed with 10% sodium chloride then dried over magnesium sulfate, filtered and concentrated under vacuum to provide the title compound (0.04 g, 43%).
Reaction SMILES: [CH:1]([C:3]1([O:8][Si:9]([CH2:14][CH3:15])([CH2:12][CH3:13])[CH2:10][CH3:11])[CH2:7][CH2:6][CH2:5][CH2:4]1)=[CH2:2].B.[OH2:17]>C1COCC1>[CH2:12]([Si:9]([CH2:10][CH3:11])([CH2:14][CH3:15])[O:8][C:3]1([CH2:1][CH2:2][OH:17])[CH2:7][CH2:6][CH2:5][CH2:4]1)[CH3:13]
Reactant: O
Reactant: C=CC1(O[Si](CC)(CC)CC)CCCC1
Agent: B
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)OC1(CCO)CCCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1-Vinyl-1-triethylsilanyloxy-cyclopentane (9.06 g; 40.0 mmole) was dissolved in dry THF (100 ml); at 0° C. borane (1M in THF; 40.0 ml; 40.0 mmole) was added dropwise and the reaction mixture was stirred for one hour at ambient temperature. At 0° C. water (50 ml)was added dropwise, followed by NaBO3.4H2O (7.69 g; 50.0 mmole) and the mixture was stirred for additional 16 hours at ambient temperature; after filtration the organic layer was removed and concentrated in vacuo; the aqu. layer was extracted with tert.-BuOMe (2×50 ml); all organic layers were combined, washed with sat. aqu. NaCl (50 ml) and dried over MgSO4. After filtration the solvent was removed in vacuo, the crude product was chromatographed on silica gel (hexane:ethyl acetate--4:1). 2-(1-Triethylsilanyloxy-cyclopentyl)-ethanol (D1) was obtained as colourless oil.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[N:4][C:3]=1[O:14][CH3:15].[CH2:16]([Sn](CCCC)(CCCC)C=C)[CH2:17]CC>O1CCOCC1.O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd](Cl)Cl>[CH3:15][O:14][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][C:2]=1[CH:16]=[CH2:17])[N:9]([CH3:12])[C:8](=[O:13])[CH2:7][CH2:6]2
Reactant: COc1nc2c(cc1Br)N(C)C(=O)CC2
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: O
Product: C=Cc1cc2c(nc1OC)CCC(=O)N2C
Temperature: 100 °C
Yield: 36.7 %

Procedure:
A mixture of 690 mg (2.5 mmol) of 7-bromo-6-methoxy-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one, 0.8 ml (2.7 mmol) of tri-n-butyl-vinyltin and 100 mg of bis(triphenylphosphine-palladium(II) chloride in 20 ml of dioxane was heated under nitrogen to 100° C. for 6 hours. The reaction mixture was cooled to room temperature and diluted with water and ethyl acetate. The ethyl acetate solution was washed with water several times. To this ethyl acetate solution was added 1 ml of saturated KF, and the mixture filtered. The filtrate was dried, evaporated, and the residue chromatographed on silica using 1 5 ethyl acetate/hexanes as the elutant. Appropriate fractions were combined and evaporated to afford 200 mg of 6-methoxy-1-methyl-7-vinyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one. 1H NMR (CDCl3) δ 7.28 (s, 1H), 6.90 (d,d 1H), 5.75 (d, 1H), 5.35 (d, 1H), 3.95 (s, 3H), 3.26 (s, 3H), 3.0 (m, 2H), 2.7 (m, 2H) Mass spectrum: m/e=219.3 (p+1).