Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][CH:27]=1)[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:18]3=[N:19][S:20](=[O:24])(=[O:23])[CH2:21][CH2:22][N:17]3[CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)[CH3:2]>C1COCC1.CO.[Pt](=O)=O>[CH2:1]([C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][CH:27]=1)[O:6][C:7]1[CH:8]=[CH:9][C:10]([CH:13]2[C:18]3=[N:19][S:20](=[O:23])(=[O:24])[CH2:21][CH2:22][N:17]3[CH2:16][CH2:15][CH2:14]2)=[CH:11][CH:12]=1)[CH3:2]
Reactant: CCc1cccc(Oc2ccc(C3=CC=CN4CCS(=O)(=O)N=C34)cc2)c1
Agent: O=[Pt]=O
Solvent: CO
Solvent: C1CCOC1
Product: CCc1cccc(Oc2ccc(C3CCCN4CCS(=O)(=O)N=C34)cc2)c1
Temperature: 50 °C
Reaction time: 4 h
Yield: 66.9 %

Procedure:
Platinum(IV) oxide (30 mg) was added to a solution of 9-[4-(3-ethylphenoxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (247 mg) in THF (dry) (20 mL) and MeOH (20 mL). The mixture was stirred at 50° C. under hydrogen for 40 min and at room temperature under hydrogen for 4 h. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) and the filtrate was concentrated in vacuo. The residue was crystallized from THF/IPE to give the title compound (167.0 mg) as colorless crystals.
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].N.CC1C2COC(=O)C=2C(O[C@@H]2O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]2O)=C(C/C=C(/CCC(O)=O)\C)C=1OC.[CH2:50]([NH2:62])[CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61]>>[CH2:1]([NH:62][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCO
Reactant: CCCCCCCCCCCCN
Agent: COc1c(C)c2c(c(O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3O)c1C/C=C(\C)CCC(=O)O)C(=O)OC2
Agent: N
Product: CCCCCCCCCCCCNCCCCCCCCCCCC

Procedure:
The same procedure as in Example 3 was repeated except for using 150 g (0.81 mol) of lauryl alcohol in place of stearyl alcohol and using ammonia in an amount of 69 g (4.06 mol), thereby conducting the reaction for 11 h. The initial maximum pressure as measured at a reaction temperature of 220° C. was 21 MPaG. The resultant reaction product was analyzed in the same manner as in Example 1. As a result, it was confirmed that the conversion of the raw alcohol was 96.3%, the selectivity to lauryl amine was 74.9%, the amount of dilauryl amine produced is 12.3%, and the amount of the other by-products produced was 10.9%.
Reaction SMILES: [NH2:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4].Cl[CH2:8][C:9]([OH:11])=[O:10].[OH-].[Na+]>O>[OH:4][CH2:3][CH:2]([CH2:5][OH:6])[NH:1][CH2:8][C:9]([OH:11])=[O:10]
Reactant: O=C(O)CCl
Reactant: NC(CO)CO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)CNC(CO)CO
Temperature: 25 °C
Reaction time: 16 h
Yield: 51.6 %

Procedure:
Serinol (2.5 g, 26 mMol), chloroacetic acid (2.41 g, 26 mMol) and NaOH (3.2 ml 10N, 52 mMol) were dissolved in 25 ml water and stirred at room temperature for 16 h. The solution was concentrated on a rotoevaporator, and the resulting glass was redissolved in methanol. Addition of acetone gave a white solid (2 g, 51%) which was recrystallised from methanol/ethyl acetate. Mass spec calculated for C5H11NO4 : 149; found: 150 (M+1); 1H NMR in D2O (0.75% TMS): 3.85 (m, 4H), 3.80 (s, 2H), 3.45 (m, 1H).
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7](Cl)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C1CCNCC1
Reactant: CC(C)(C)c1ccc(C#N)c(Cl)n1
Product: CC(C)(C)c1ccc(C#N)c(N2CCCCC2)n1
Temperature: 25 °C
Reaction time: 20 h
Yield: 96.1 %

Procedure:
A mixture of 6-tert-butyl-2-chloronicotinonitrile (Tetrahedron 1965, 21, 2453-2467, 1.5 g, 7.7 mmol) and piperidine (15 ml, 176 mmol) was stirred for 20 hours at room temperature. Then the reaction mixture was evaporated to remove piperidine in vacuo to give the title compound (1.8 g, 98%).
Reaction SMILES: [CH2:1]([OH:21])[CH2:2][CH:3]([CH2:5][CH2:6][CH2:7][CH:8]([CH2:10][CH2:11][CH2:12][CH:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])[CH3:4].[Cl:22][C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.N1C=CC=CC=1>ClCCl>[Cl:22][C:23]([O:21][CH2:1][CH2:2][CH:3]([CH2:5][CH2:6][CH2:7][CH:8]([CH2:10][CH2:11][CH2:12][CH:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])[CH3:4])=[O:25]
Reactant: CC(C)CCCC(C)CCCC(C)CCCC(C)CCO
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)CCCC(C)CCCC(C)CCCC(C)CCOC(=O)Cl
Yield: 264.6 %

Procedure:
Phytanol (48.8 g, 163.5 mmol), and triphosgene (16.17 g, 54.66 mmol) were dissolve in 300 ml of dichloromethane, stirred and cooled on an ice bath. Anhydrous pyridine (12.93 g, 163.5 mmol) was added dropwise over a period of 1 hour. The reaction mixture was stirred for an additional 1 h at room temperature, and then quickly extracted with extra methylene chloride and ice water. The organic layer was pooled, dried over Na2SO4 and evaporated to dryness to yield 52.22 g (88.7%) of phytanyl chloroformate as yellow liquid. 1H NMR in CDCl3: δ0.83, 0.85, 0.86, 0.88, (4s, each 3H, CH3), 0.91 (d, 3H, J=6.0 Hz, CH3), 0.95-1.40 (m, 20H, CH2), 1.39-1.68 (m, 4H, CH), 1.68-1.88 (m, 1H, OH), 4.27-4.47 (m, 2H, CH2OH).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.O.[CH3:12][O:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1.Cl>C(OCCO)C>[CH3:12][O:13][C:14]1[CH:20]=[CH:19][C:17]([NH:18][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:16][CH:15]=1
Reactant: COc1ccc(N)cc1
Reactant: O=[N+]([O-])c1cccnc1Cl
Agent: Cl
Solvent: CCOCCO
Solvent: O
Product: COc1ccc(Nc2ncccc2[N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 84.1 %

Procedure:
5.0 g (32 mmol) of 2-chloro-3-nitropyridine was dissolved in 2-ethoxyethanol (150 mL), and water (150 mL) was added thereto. To the mixed solution, 3.9 g (32 mmol) of 4-methoxyaniline and 6 N hydrochloric acid (1 mL) were added, and the mixture was heated to reflux for 12 hours while stirring. After confirming the completion of the reaction, the reaction solution was cooled to room temperature, and the solvent was distilled off under reduced pressure. The residue was extracted with ethyl acetate, and washed with saturated brine, and then the obtained organic layer was dried over anhydrous magnesium sulfate. The inorganic matter was separated by filtration, and then the solvent was distilled off under reduced pressure, to obtain 6.6 g (yield: 85%) of N-(4-methoxyphenyl)-3-nitropyridin-2-amine as orange-colored crystals.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:18].[CH3:19][O:20][C:21]1[CH:22]=[C:23]([C:29]2[C@@H:38]3[C@@H:33]([CH2:34][CH:35]=[CH:36][CH2:37]3)[C:32](=[O:39])[N:31]([CH:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)[N:30]=2)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:19][O:20][C:21]1[CH:22]=[C:23]([C:29]2[C@@H:38]3[C@@H:33]([CH2:34][CH:35]=[CH:36][CH2:37]3)[C:32](=[O:39])[N:31]([CH:40]3[CH2:45][CH2:44][N:43]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]4[C:16](=[O:17])[C:15]5[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=5)[C:9]4=[O:18])[CH2:42][CH2:41]3)[N:30]=2)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28]
Reactant: COc1ccc(C2=NN(C3CCNCC3)C(=O)[C@@H]3CC=CC[C@H]23)cc1OC
Reactant: O=C1c2ccccc2C(=O)N1CCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(C2=NN(C3CCN(CCCCCCN4C(=O)c5ccccc5C4=O)CC3)C(=O)[C@@H]3CC=CC[C@H]23)cc1OC
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 6 mmol of 2-(6-bromo-hexyl)-isoindole-1,3-dione, 6 mmol of compound 5c and 3 g of potassium carbonate in 50 ml of dimethylformamide is stirred for 18 h at RT. After evaporating the solvent, the residue is partitioned between water and ethyl acetate. The organic layer is dried over magnesium sulfate and evaporated. The residue is purified by chromatography (ethyl acetate:hexane/4:1). M. p. 39-44° C.
Reaction SMILES: Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[O:14][CH2:13][CH2:12][NH:11][CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl[C:23]1[N:28]([CH3:29])[C:27](=[O:30])[CH:26]=[C:25]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([Cl:37])[C:32]=2[Cl:38])[N:24]=1>O1CCCC1>[Cl:37][C:33]1[C:32]([Cl:38])=[C:31]([C:25]2[N:24]=[C:23]([N:11]3[CH2:12][CH2:13][O:14][C@@H:9]([C:6]4[CH:5]=[CH:4][C:3]([F:2])=[CH:8][CH:7]=4)[CH2:10]3)[N:28]([CH3:29])[C:27](=[O:30])[CH:26]=2)[CH:36]=[CH:35][N:34]=1
Reactant: Fc1ccc([C@H]2CNCCO2)cc1
Reactant: Cn1c(Cl)nc(-c2ccnc(Cl)c2Cl)cc1=O
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cn1c(N2CCO[C@@H](c3ccc(F)cc3)C2)nc(-c2ccnc(Cl)c2Cl)cc1=O
Reaction time: 12 h
Yield: 68.8 %

Procedure:
To a solution of (2S)-2-(4-fluorophenyl)morpholine hydrochloride (0.8 g, 3.68 mmol) and triethylamine (2.1 g, 20.8 mmol) in tetrahydrofuran (20 ml) was added 2-chloro-6-(2,3-dichloropyridin-4-yl)-3-methyl-3H-pyrimidin-4-one (2.0 g, 6.88 mmol) portionwise and the mixture was stirred for 12 hours. The resulting suspension was partitioned between chloroform and 1N sodium hydroxide and the aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish 6-(2,3-dichloropyridin-4-yl)-2-((2S)-2-(4-fluorophenyl)morpholin-4-yl)-3-methyl-3H-pyrimidin-4-one (1.1 g, 2.53 mmol, 69%) as white crystals.
Reaction SMILES: [Br:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([OH:9])=O)[N:6]=1.[CH3:10][S:11]([NH2:14])(=[O:13])=[O:12].N12CCCN=C1CCCCC2>O1CCCC1>[Br:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:14][S:11]([CH3:10])(=[O:13])=[O:12])=[O:9])[N:6]=1
Reactant: CS(N)(=O)=O
Reactant: O=C(O)c1csc(Br)n1
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: CS(=O)(=O)NC(=O)c1csc(Br)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 91.1 %

Procedure:
2-Bromo-1,3-thiazole-4-carboxylic acid (0.8 g, 3.85 mmol) was initially charged in tetrahydrofuran (10 ml). N,N′-Carbonyldiimidazole (0.94 g, 5.77 mmol) was added and the reaction mixture was heated under reflux for 1 h. Methanesulphonamide (0.55 g, 5.77 mmol) was added and, after 10 min, 1,8-diazabicyclo[5.4.0]undec-7-ene (0.88 g, 5.77 mmol). The reaction mixture was stirred at room temperature for 16 h and then the solvent was removed under reduced pressure. The residue was taken up in water and acidified with hydrochloric acid. The precipitated product was filtered off with suction. The aqueous phase was extracted with dichloromethane; the organic phase was dried over sodium sulphate and filtered, and the solvent was removed under reduced pressure. This gave a total of 1.0 g (89% of theory) of 2-bromo-N-(methylsulphonyl)-1,3-thiazole-4-carboxamide.
Reaction SMILES: [H-].[Li+:2].[C:3]([C:5]([C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:6]([OH:17])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])#[N:4].C1COCC1>CCOCC>[Li+:2].[C:3]([C:5]([C:18](=[O:23])[C:19]([CH3:21])([CH3:20])[CH3:22])=[C:6]([O-:17])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])#[N:4]
Reactant: CC(C)(C)C(=O)C(C#N)=C(O)c1ccc(Cl)cc1[N+](=O)[O-]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)C(C#N)=C([O-])c1ccc(Cl)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 81.8 %

Procedure:
To a stirred slurry of 0.36 g of LiH in 15 ml of dry ether under N2 at room temperature was rapidly added a solution of 1.5 g of 2-cyano-4,4-dimethyl-1-hydroxy-3-oxo-1-(2-nitro-4-chlorophenyl)-1-pentene dissolved in 15 ml of dry ether. The reaction mixture turned brown and a precipitate formed with 5 min. Enough dry THF was added to dissolve the solid and the mixture allowed to stir overnight at ambient temperature. The reaction was filtered and the filtrate concentrated under reduced pressure to yield 1.25 g of product as a yellow solid, m.p. >230° C. (decomp.).
Reaction SMILES: C([O:5][C:6]([CH:8]1[CH:14]([CH2:15][OH:16])[CH2:13][CH2:12][CH2:11][CH2:10][N:9]1[S:17]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)(=[O:19])=[O:18])=[O:7])(C)(C)C.ClC(Cl)(Cl)C(=N)O[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.FC(F)(F)S(O)(=O)=O>C1CCCCC1.ClCCl>[CH2:32]([O:16][CH2:15][CH:14]1[CH2:13][CH2:12][CH2:11][CH2:10][N:9]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH:8]1[C:6]([OH:5])=[O:7])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: N=C(OCc1ccccc1)C(Cl)(Cl)Cl
Reactant: COc1ccc(S(=O)(=O)N2CCCCC(CO)C2C(=O)OC(C)(C)C)cc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: C1CCCCC1
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)N2CCCCC(COCc3ccccc3)C2C(=O)O)cc1
Temperature: 0 °C

Procedure:
To a solution of 3-Hydroxymethyl-1-(4-methoxy-benzenesulfonyl)-azepane-2-carboxylic acid tert-butyl ester (110 mg, 0.275 mmoL) in 3.9 mL cyclohexane and 1.95 mL of dichloromethane was added benzyl trichloracetimidate (0.1 mL, 0.55 mmoL). The solution was cooled to 0° C. and trifluoromethane sulfonic acid (0.008 mL, 0.091 mmoL) was added in. After 2.5 hours the reaction was filtered and the cake was washed with a 2:1 solution of cyclohexane and dichloromethane, the solvent was evaporated under reduced pressure and the residue was taken up in ethyl acetate. The solution was washed sequentially with dilute sodium bicarbonate and brine. The organic layer was dried over anhyrous magnesium sulfate, filtered, and the solvent evaporated under reduced pressure. The residue was purified by column chromatography (silica: 30% ethyl acetate in hexanes to 5% methanol in dichloromethane) to yield 3-Benzyloxymethyl-1-(4-methoxy-benzenesulfonyl)-azepane-2-carboxylic acid; MS: (M+H)+ =434, (M-H)- =432.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].CN(C=O)C.S(Cl)([Cl:23])(=O)=O>C(Cl)(Cl)Cl>[Cl:23][C:12]1[S:11][C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[N:14][CH:13]=1
Reactant: O=[N+]([O-])c1cccc(-c2nccs2)c1
Reactant: O=S(=O)(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1cccc(-c2ncc(Cl)s2)c1

Procedure:
To a stirred solution of 2-(3-nitro-phenyl)-thiazole (18.5 g, 89.7 mmol) in a mixture of chloroform (150 ml) and anhydrous DMF (40 ml) was slowly added sulfuryl chloride (28.2 ml, 359 mmol). After the addition, the resultant mixture was stirred at reflux for 3 hours. The cooled mixture was concentrated under reduced pressure and the residue was partitioned between aqueous calcium chloride (3M) and ethyl acetate. The organic layer was washed with aqueous sodium carbonate, dried over magnesium sulphate and evaporated to dryness to leave the desired product. 20.6 g (80%).
Reaction SMILES: C(O[C:6]([C:8]1[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:11]2[CH2:12][CH:13]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:10]=2[CH:9]=1)=[O:7])(C)(C)C.[CH3:29][N:30]1[CH:34]=[CH:33][C:32]([NH2:35])=[N:31]1>O>[CH3:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35][C:6]([C:8]2[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:11]3[CH2:12][CH:13]([CH2:15][O:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[O:14][C:10]=3[CH:9]=2)=[O:7])=[N:31]1
Reactant: Cn1ccc(N)n1
Reactant: CC(C)Oc1cc(C(=O)OC(C)(C)C)cc2c1CC(COc1ccccc1)O2
Solvent: O
Product: CC(C)Oc1cc(C(=O)Nc2ccn(C)n2)cc2c1CC(COc1ccccc1)O2

Procedure:
The title compound was prepared in a similar manner as described for Example 200 from 4-isopropoxy-2-phenoxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester (214c) and 1-methyl-3-aminopyrazole. 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1 H) 7.28-7.32 (m, 3 H) 7.05 (s, 1 H) 6.93-7.00 (m, 3 H) 6.89 (s, 1 H) 6.84 (s, 1 H) 5.19-5.27 (m, 1 H) 4.64-4.72 (m, 1 H) 4.20-4.26 (m, 1 H) 4.11 (dd, J=9.98, 4.67 Hz, 1 H) 3.82 (s, 3 H) 3.35 (dd, J=16.42, 9.35 Hz, 1 H) 3.11 (dd, J=16.55, 6.95 Hz, 1 H) 1.36 (d, J=5.81 Hz, 6 H); LCMS for C23H25N3O4 m/z 408.20 (M+H)+; Anal. Calcd. for C23H25N3O4.0.50 H2O: C, 66.33; H, 6.29; N, 10.09. Found: C, 66.29; H, 6.05; N, 9.87.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][O-:11].[Na+]>C1COCC1.CO>[Cl:1][C:2]1[N:7]=[C:6]([O:11][CH3:10])[C:5]([F:9])=[CH:4][N:3]=1
Reactant: C[O-]
Reactant: Fc1cnc(Cl)nc1Cl
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: COc1nc(Cl)ncc1F
Temperature: -10 °C
Reaction time: 21 h
Yield: 7.4 %

Procedure:
2,4-Dichloro-5-fluoropyrimidine (515 mg, 3.08 mmol) was weighed into a 150 mL RBF, and was suspended in THF (5.0 mL). The stirring suspension was cooled to −10° C. NaOMe (250 mg, 4.63 mmol) was added in one portion at −10° C. An additional 0.5 eq of NaOMe were added and the suspension was stirred at RT for 21 h. The suspension was diluted with MeOH, and the solvents were removed in vacuo. The crude material was purified by flash chromatography (eluting with 100% DCM) to give 2-chloro-5-fluoro-4-methoxypyrimidine (37 mg, 0.228 mmol, 7.38%) as an amorphous white solid. MS (ESI, pos. ion) m/z: 162.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (d, J=2.7 Hz, 1H), 4.04 (s, 3H).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[C:8]([CH2:9][OH:10])=[CH:7][N:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:5]=1.F[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1.O>CN(C)C=O>[CH3:3][C:4]1[C:8]([CH2:9][O:10][C:18]2[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=2)=[CH:7][N:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:5]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: Cc1nn(-c2ccccn2)cc1CO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nn(-c2ccccn2)cc1COc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
Sodium hydride (60%, oily, 0.80 g) was added to a solution of [3-methyl-1-(2-pyridyl)-1H-pyrazol-4-yl]methanol (3.20 g) in N,N-dimethylformamide (50 ml) at 0° C., and the mixture was stirred at room temperature for one hour. 4-fluorobenzaldehyde (2 ml) was added to the reaction mixture, and the mixture was stirred overnight at 50° C. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and then concentrated. The residue was subjected to silica gel column chromatography, and 4-[3-methyl-1-(2-pyridyl)-1H-pyrazol-4-ylmethoxy]benzaldehyde (4.26 g, yield: 86%) was obtained as colorless crystals from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). This was recrystallized from ethyl acetate-hexane. Melting point: 84–85° C.
Reaction SMILES: [C:1]1([C:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][N:9]=[C:10]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:11]([O-])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([NH+](CC)CC)C.C(Cl)(=O)C([Cl:41])=O.CN(C)C=O>C(Cl)Cl>[C:1]1([C:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][N:9]=[C:10]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:11]([Cl:41])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C([O-])C(=NOC(c1ccccc1)(c1ccccc1)c1ccccc1)c1cccs1
Agent: CC[NH+](CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)C(=NOC(c1ccccc1)(c1ccccc1)c1ccccc1)c1cccs1
Reaction time: 2 h
Yield: 103 %

Procedure:
A solution of triethylammonium 2-triphenylmethoxyimino-2-(thien-2-yl)-acetate (syn isomer) (2.30 g, 4.46 mmole) in dry methylene chloride (50 ml) was cooled to 0° to +5° and stirred whilst oxalyl chloride (0.38 ml, 4.46 mmole) was added. N,N-Dimethylformamide (ca 0.1 ml) was added and the mixture was stirred at 0° to +5° for 21/2 hours. The solvent was evaporated and the residue was stirred with ether (100 ml) for 1 hour, and the suspension then filtered. The filtrate and ether washings (100 ml) were evaporated to give the title compound as a white crystalline solid (1.985 g, quantitative). This acid chloride was used without further purification.
Reaction SMILES: [CH3:1][C:2]([NH2:6])([CH3:5])[CH2:3][NH2:4].[CH3:7][C:8]([CH3:13])=[CH:9][C:10](O)=[O:11].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:7][C:8]1([CH3:13])[NH:6][C:2]([CH3:5])([CH3:1])[CH:3]=[N:4][C:10](=[O:11])[CH2:9]1
Reactant: CC(C)(N)CN
Reactant: CC(C)=CC(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC1(C)C=NC(=O)CC(C)(C)N1

Procedure:
4.4 g 2-methyl-1,2-propanediamine, 6.0 g 3,3-dimethylacrylic acid and 8 ml toluene were mixed and heated at 140°-150° C. overnight. The mixture was cooled and poured into 80 ml of 5% Na2CO3 solution; then extracted 3 times with 50 ml aliquots of chloroform. The combined chloroform solutions were dried and concentrated. Upon recrystallization from hexane-benzene a yellow crystalline solid, m. pt 129°-132° C., is obtained.
Reaction SMILES: C[O:2][C:3]1(OC)[CH2:8][CH2:7][O:6][CH2:5][CH:4]1[OH:9].[CH3:12]C([O-])(C)C.[Na+].COS(OC)(=O)=O>C1COCC1>[CH3:12][O:9][C@H:4]1[C:3](=[O:2])[CH2:8][CH2:7][O:6][CH2:5]1
Reactant: COC1(OC)CCOCC1O
Reactant: CC(C)(C)[O-]
Agent: [Na+]
Solvent: COS(=O)(=O)OC
Solvent: C1CCOC1
Product: CO[C@@H]1COCCC1=O

Procedure:
reacting said 4,4-dimethoxytetrahydro-2H-pyran-3-ol in the presence of THF, NaOt-Bu, Me2SO4, and an acid to form (3R)-3-methoxytetrahydro-4H-pyran-4-one.
Reaction SMILES: [F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([N:13]([CH3:42])[C:14]([N:16]([CH3:41])[C@H:17]2[C@H:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:20][N:19]([C:29](OC3C=CC([N+]([O-])=O)=CC=3)=[O:30])[CH2:18]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:45]1[CH2:50][CH2:49][S:48][CH2:47][CH2:46]1>>[F:1][C:2]([F:43])([F:44])[C:3]1[CH:4]=[C:5]([N:13]([CH3:42])[C:14]([N:16]([C@H:17]2[C@H:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:20][N:19]([C:29]([N:45]3[CH2:50][CH2:49][S:48][CH2:47][CH2:46]3)=[O:30])[CH2:18]2)[CH3:41])=[O:15])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1
Reactant: CN(C(=O)N(C)[C@@H]1CN(C(=O)Oc2ccc([N+](=O)[O-])cc2)C[C@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: C1CSCCN1
Product: CN(C(=O)N(C)[C@@H]1CN(C(=O)N2CCSCC2)C[C@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1

Procedure:
By reaction and purification in the same manner as in the method described in Example 420 and using the compound obtained in Example 362 and thiomorpholine, the title compound was obtained.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])[CH3:3].[O-]CC.[Na+].Cl[C@@H:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[S:27][CH2:28][C:29]([OH:31])=[O:30].Cl>C(O)C.O>[CH3:4][C:2]([C:5]1[CH:10]=[C:9]([S:11][C@@H:22]2[CH2:26][CH2:25][CH2:24][C@H:23]2[S:27][CH2:28][C:29]([OH:31])=[O:30])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:1])[CH3:3]
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Reactant: O=C(O)CS[C@@H]1CCC[C@H]1Cl
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(C)(C)c1cc(S[C@@H]2CCC[C@H]2SCC(=O)O)cc(C(C)(C)C)c1O
Reaction time: 1.5 h

Procedure:
2.6-bis(1.1-Dimethylethyl)-4-mercaptophenol (0.73 g, 0.0031 mole) was added to freshly prepared sodium ethoxide [sodium (0.16 g, 0,007 mole)] in ethanol (10 ml). Once dissolved, the product of Example 4 (0.50 g, 0.0026 mole) was added and the reaction mixture was stirred for 90 minutes and poured into water (50 ml) containing 1N hydrochloric acid (25 ml). The mixture was extracted three times with 20 ml of diethyl ether, and the combined extracts were washed with water (20 ml), dried over anhydrous magnesium sulfate, filtered and concentrated to an oil with a rotary evaporator. The product was purified by silica gel chromatography. The structure was supported by NMR and elemental analysis.