Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S1C=CC=C1.C(O)C.[F:9][C:10]1[CH:38]=[CH:37][C:13]([C:14]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][NH:25][C:26](=[O:36])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N+:33]([O-])=O)[CH2:18][CH2:17]2)=[O:15])=[CH:12][CH:11]=1.[H][H]>[Pt].CO>[NH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:26]([NH:25][CH2:24][CH2:23][CH2:22][N:19]1[CH2:20][CH2:21][CH:16]([C:14](=[O:15])[C:13]2[CH:12]=[CH:11][C:10]([F:9])=[CH:38][CH:37]=2)[CH2:17][CH2:18]1)=[O:36]
Reactant: O=C(NCCCN1CCC(C(=O)c2ccc(F)cc2)CC1)c1ccccc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pt]
Solvent: c1ccsc1
Solvent: CCO
Solvent: CO
Product: Nc1ccccc1C(=O)NCCCN1CCC(C(=O)c2ccc(F)cc2)CC1
Yield: 45 %

Procedure:
To 1 part of a solution of 2 parts of thiophene in 40 parts of ethanol are added 18 parts of N-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2-nitrobenzamide and 200 parts of methanol. The whole is hydrogenated at normal pressure and at room temperature with 2 parts of platinum-on-charcoal catalyst 5%. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is crystallized from 2-propanol. The product is filtered off and dried, yielding 7.5 parts (45%) of 2-amino-N-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]benzamide; mp. 113.2° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[OH-].[K+].[CH3:11]O>CS(C)=O>[CH3:11][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[N:4][CH:3]=1
Reactant: CO
Reactant: Cc1ccc(O)cn1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: COc1ccc(C)nc1
Temperature: 20 °C
Reaction time: 15 h
Yield: 56 %

Procedure:
150 ml of 3-hydroxy-6-methylpyridine are metered into a solution of 84 g of potassium hydroxide in 400 ml of methanol and 500 ml of dimethyl sulfoxide in the course of one hour. After removal of the methanol on a rotary evaporator, 213 g of methyl iodide, dissolved in 100 ml of dimethyl sulfoxide, are added dropwise, while cooling with ice, and the reaction mixture is stirred at 20° C. for 15 hours and subjected to steam distillation. The distillate is extracted continuously in the extractor with methylene chloride and the extract is concentrated. 85 g (56% of theory) of 5-methoxy-2-methylpyridine are obtained as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.[NH2:11][C:12]1[CH:16]=[CH:15][NH:14][N:13]=1.O=[C:18]([CH2:25][CH2:26][CH3:27])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>>[Cl:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:5]2[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([CH2:25][CH2:26][CH3:27])[NH:11][C:12]3=[N:13][NH:14][CH:15]=[C:16]23)[CH:7]=[CH:8][CH:9]=1
Reactant: CCCC(=O)CC(=O)OCC
Reactant: Cc1c(Cl)cccc1C=O
Reactant: Nc1cc[nH]n1
Product: CCCC1=C(C(=O)OCC)C(c2cccc(Cl)c2C)c2c[nH]nc2N1

Procedure:
The title compound was prepared from 3-chloro-2-methylbenzaldehyde, 3-aminopyrazole and ethyl 3-ketohexanoate in the same manner as in Example 1.
Reaction SMILES: [OH:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[O:20])[CH2:10][CH2:9]4)[CH:6]=[CH:5][C:4]=2[CH:3]=1.[C:21]1(C)C=[CH:25][C:24](S(O)(=O)=O)=[CH:23][CH:22]=1.[O:32]1CCCC1>O1C=CCCC1.C(OCC)(=O)C>[O:32]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[O:20])[CH2:10][CH2:9]4)[CH:6]=[CH:5][C:4]=2[CH:3]=1
Reactant: C[C@]12CC[C@@H]3c4ccc(O)cc4C=C[C@H]3[C@@H]1CCC2=O
Reactant: C1CCOC1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: C1=COCCC1
Solvent: CCOC(C)=O
Product: C[C@]12CC[C@@H]3c4ccc(OC5CCCCO5)cc4C=C[C@H]3[C@@H]1CCC2=O

Procedure:
A suspension of 2.6 g of 3-hydroxy-estra-1,3,5(10),6-tetraen-17-one in 26 ml of tetrahydrofuran and 2.6 ml of dihydropyran is stirred with 12.3 mg of para-toluenesulfonic acid for 3 hours at room temperature. Then, it is diluted with ethyl acetate, washed with sodium bicarbonate solution as well as with saturated sodium chloride solution, dried on sodium sulfate and concentrated by evaporation in a vacuum. 3.0 g of 3-tetrahydropyranyloxy-estra-1,3,5(10),6-tetraen-17-one is obtained as colorless crystals.
Reaction SMILES: C[O:2][C:3]([P:5]([OH:8])([OH:7])=[O:6])=O.[CH3:9][NH:10][NH2:11]>O.CO.C(O)C>[CH3:9][N:10]([C:3]([P:5]([OH:8])([OH:7])=[O:6])=[O:2])[NH2:11]
Reactant: CNN
Reactant: COC(=O)P(=O)(O)O
Solvent: CCO
Solvent: CO
Solvent: O
Product: CN(N)C(=O)P(=O)(O)O
Temperature: 80 °C
Reaction time: 7 h
Yield: 38 %

Procedure:
46 parts by weight of Na2 -salt of phosphonoformic acid methyl ester are dissolved in 90 parts by volume of water and 46 parts by weight of methyl hydrazine are added at 25° C. The mixture is stirred at 80° C. for 7 hours and allowed to cool. The residue is removed by suction filtration and the filtrate is evaporated in vacuo. The residue after evaporation is digested with ethyl alcohol and the such obtained crystals are again dissolved in a mixture of 70 parts by volume methanol and 200 parts by volume ethyl alcohol and thereafter precipitated. 90 parts by weight of Na2 -salt of phosphonoformic acid methyl hydrazide are obtained (yield 38%).
Reaction SMILES: [CH3:1][C:2]([N:5]1[C:10](=[O:11])[CH2:9][C:8](=[O:12])[N:7]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[C:6]1=[O:24])([CH3:4])[CH3:3].C([N:29]=[C:30]=[O:31])(C)(C)C.C(C1C=CC(CN)=CC=1)(C)(C)C.Cl[C:45](Cl)([C:49]([O-:51])=[O:50])C([O-])=O>ClCCl>[CH3:4][C:2]([N:5]1[C:10]([OH:11])=[C:9]([C:30]([NH:29][CH2:45][C:49]([OH:51])=[O:50])=[O:31])[C:8](=[O:12])[N:7]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[C:6]1=[O:24])([CH3:1])[CH3:3]
Reactant: CC(C)(C)N=C=O
Reactant: O=C([O-])C(Cl)(Cl)C(=O)[O-]
Reactant: CC(C)(C)c1ccc(CN2C(=O)CC(=O)N(C(C)(C)C)C2=O)cc1
Agent: CC(C)(C)c1ccc(CN)cc1
Solvent: ClCCl
Product: CC(C)(C)c1ccc(Cn2c(=O)c(C(=O)NCC(=O)O)c(O)n(C(C)(C)C)c2=O)cc1
Reaction time: 1 h
Yield: 79 %

Procedure:
1-(1,1-Dimethylethyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-2,4,6(1H,3H,5H)-pyrimidinetrione. A mixture of t-butyl isocyanate (571 uL, 5.0 mmoles) and 4-t-butylbenzylamine (880 uL, 5.0 mmoles) in dry dichloromethane was stirred for 1 hour. Dichloromalonate (486 uL, 5.0 mmoles) was added and the mixture was heated under reflux for 1 hour. The mixture was washed with 1N hydrochloric acid and evaporated onto silica gel. Flash chromatography (10-35% ethyl acetate-hexane) gave the title compound (1.3 g, 79%) 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 9 H) 1.63 (s, 9 H) 3.60 (s, 2 H) 4.99 (s, 2 H) 7.37 (d, J=2.78 Hz, 4 H).
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([Cl:24])[C:11]3[CH:15]([CH2:16][C:17]([O:19]CC)=[O:18])[O:14][B:13]([OH:22])[C:12]=3[CH:23]=2)=[N:4][N:3]=1.[Li+].[OH-].Cl>C1COCC1.O>[NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([Cl:24])[C:11]3[CH:15]([CH2:16][C:17]([OH:19])=[O:18])[O:14][B:13]([OH:22])[C:12]=3[CH:23]=2)=[N:4][N:3]=1
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3nnc(N)s3)cc(Cl)c21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Nc1nnc(Oc2cc(Cl)c3c(c2)B(O)OC3CC(=O)O)s1
Temperature: 0 °C
Reaction time: 3 h
Yield: 4.9 %

Procedure:
To a solution of ethyl 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-4-chloro-1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)acetate (330 mg, 0.89 mmol) in THF (10 mL) and H2O (3 mL) was added LiOH (100 mg, 4.16 mmol). The reaction mixture was stirred at 0° C. for 3 h and acidified with 1N HCl to pH=2-4. The resulting mixture was extracted with EtOAc (2×10 ml). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by prep HPLC to give the title compound as a white powder (15 mg, yield 5%). 1H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 9.57 (s, 1H), 7.56 (m, 2H), 7.20 (s, 2H), 5.51 (m, 1H), 3.22 (m, 1H), 2.32 (s, 3H), 2.36 (m, 1H). MS (ESI) m/z=342 [M+H]+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:30]([O:32][CH2:33][CH3:34])=[CH2:31])CCC.C(OC=C)=C>CN(C=O)C.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>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:30]([O:32][CH2:33][CH3:34])=[CH2:31])[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCNC(=O)Nc1nc2cc(OCc3ccccc3)cc(Br)c2s1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C=COC=C
Solvent: CN(C)C=O
Product: C=C(OCC)c1cc(OCc2ccccc2)cc2nc(NC(=O)NCC)sc12
Temperature: 100 °C

Procedure:
1-(5-benzyloxy-7-bromo-1,3-benzothiazol-2-yl)-3-ethyl-urea (1 g, 2.46 mmol) and tributyl-(1-ethoxy-vinyl)-stannane (1.77 g, 4.92 mmol) were dissolved in DMF (30 mL) and the mixture deoxygenated by bubbling N2 through the solution for 20 min. Pd(PPh3)4, (284 mg, 0.246 mmol) was added and the reaction heated to 100° C. for 4 h under a N2 atmosphere, at the end of which time LCMS indicated clean formation of the vinyl ether. The reaction was concentrated under reduced pressure, diluted with EtOAc, washed with water then brine and the organic layer dried (MgSO4), filtered and the solvent removed in vacuo to give the desired compound.
Reaction SMILES: [CH2:1]([C:3]1[CH:31]=[CH:30][C:6]([C:7]([N:9]2[CH2:14][CH2:13][C:12]3([O:19][C:18]4[CH:20]=[C:21]([C:24](O)=[O:25])[CH:22]=[CH:23][C:17]=4[N:16]4[CH:27]=[CH:28][CH:29]=[C:15]34)[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[O:32][CH3:33])[CH3:2].[CH3:34][N:35](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:36].F[P-](F)(F)(F)(F)F.Cl.CNC.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([C:3]1[CH:31]=[CH:30][C:6]([C:7]([N:9]2[CH2:14][CH2:13][C:12]3([O:19][C:18]4[CH:20]=[C:21]([C:24]([N:35]([CH3:36])[CH3:34])=[O:25])[CH:22]=[CH:23][C:17]=4[N:16]4[CH:27]=[CH:28][CH:29]=[C:15]34)[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[O:32][CH3:33])[CH3:2]
Reactant: CCc1ccc(C(=O)N2CCC3(CC2)Oc2cc(C(=O)O)ccc2-n2cccc23)cc1OC
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CNC
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCc1ccc(C(=O)N2CCC3(CC2)Oc2cc(C(=O)N(C)C)ccc2-n2cccc23)cc1OC

Procedure:
A solution of 1′-(4-ethyl-3-methoxybenzoyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-7-carboxylic acid (40 mg, 0.09 mmol), HATU (34 mg, 0.090 mmol), N,N-dimethylamine hydrochloride (7.3 mg, 0.090 mmol) and iPr2NEt (62 μL, 0.36 mmol) in DMF (1 mL) was stirred at room temperature overnight. The reaction mixture was filtered and purified by reverse phase LC-MS (10-99% CH3CN/H2O). Pure fractions were combined and evaporated to yield 1′-(4-ethyl-3-methoxybenzoyl)-N,N-dimethylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-7-carboxamide. ESI-MS m/z calc. 473.6, found 474.5 (M+1)+; Retention time: 1.80 minutes (3 min run).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[CH3:28][S:29]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30]>>[CH3:28][S:29]([C:32]1[CH:37]=[C:36]([C:2]2[CH:7]=[C:6]([C:8]3[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=4)[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:35]=[CH:34][CH:33]=1)(=[O:31])=[O:30]
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3ccnc(Cl)c3)n2)cc1
Product: CS(=O)(=O)c1cccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)ccn2)c1

Procedure:
The title compound was prepared from 2-(2-chloro-pyridin-4-yl)-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.6) (0.404 g, 1.0 mmol) and commercially available 3-methanesulfonyl-phenylboronic acid (0.22 g, 1.1 mmol) according to the general procedure VI. Obtained as a white solid (0.4 g, 77%). MS (ISP) 524.0 [(M+H)+]; mp 238.5° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[O:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:27][CH:24]2[CH2:25][CH2:26][O:21][CH2:22][CH2:23]2)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: NC1CCOCC1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cnc(Cl)nc1NC1CCOCC1
Temperature: -64 °C
Reaction time: 5 h
Yield: 78.1 %

Procedure:
To a solution of 2,4-dichloro-5-nitropyrimidine (1.03 g, 5.15 mmol) in THF (40 mL) at −78° C., DIPEA (2.0 mL, 11.86 mmol) and tetrahydro-2H-pyran-4-amine (0.54 mL, 5.15 mmol) were added. The reaction mixture was stirred from −78 to −50° C. for 5 h. The crude mixture was quenched with H2O (50 mL), extracted with EtOAc (3×40 mL) and the combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated. The crude product thus obtained was chromatographed over silica gel using EtOAc/hexanes mixtures of increasing polarity as eluent, to afford 1.04 g of the desired compound (78% yield).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([NH:13][CH3:14])[C@@H:10]([OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[CH3:18]O>>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@H:10]([OH:15])[C@@H:11]([N:13]([CH3:18])[CH3:14])[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CO
Reactant: CN[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1O
Agent: [Na+]
Agent: [OH-]
Product: CN(C)[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1O
Reaction time: 1 h

Procedure:
This compound was prepared in the same manner as in Reference Example 25 (step 1), except that (3S,4S)-1-(t-butoxycarbonyl)-3-hydroxy-4-(methylamino)pyrrolidine (Tetrahedron: Asymmetry, 2001, 12, 2989-2997) was used, and that the reaction was conducted for 1 hour under ice cooling, the reaction solution was alkalified with a 1N aqueous sodium hydroxide solution and methanol was mostly distilled off under reduced pressure, followed by extraction with ethyl acetate twice.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8](O)[CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.CS([Cl:28])(=O)=O>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([Cl:28])[CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: O[C@@H](CN1CCOCC1)c1ccc(Br)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cl[C@@H](CN1CCOCC1)c1ccc(Br)cc1
Temperature: 0 °C
Yield: 66.6 %

Procedure:
(1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethanol (48.5 g, 0.17 mol) was dissolved in 200 mL CH2Cl2 at room temperature with magnetic stirring and triethylamine (52 mL. 0.37 mol, 2.2 equiv) was added. The resulting solution was cooled to 0° C. and treated with methanesulfonyl chloride (16 mL, 0.20 mol, 1.2 equiv) through an addition funnel. After the addition, the reaction mixture was maintained at 40° C. for 48 h with magnetic stirring. The reaction mixture was concentrated and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude brown oil was purified by silica gel chromatography (800 g silica gel 60, 230-400 mesh, 5% EtOAc/CH2Cl2 as eluent). Concentration of the pure fractions yielded the title compound as a yellow oil (34.5 g, 67%). MS (ES) m/e 304 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH2:9]=C.[BH4-].[Na+].[OH-].[Na+].[C:15](O)(=O)[CH3:16]>>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH:15]([CH3:16])[CH3:9])=[CH:4][CH:3]=1
Reactant: Nc1ccc(F)cc1
Reactant: C=C
Reactant: CC(=O)O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Product: CC(C)Nc1ccc(F)cc1
Temperature: 10 °C
Reaction time: 1 h
Yield: 71 %

Procedure:
A solution of 22.2 g (0.2 m) 4-fluoroaniline, and 17.6 ml (0.24 m) acetene in 120 ml (0.2 m) glacial acetic acid in the three neck 500 ml round bottom flask was stirred mechanically and cooled to approximately 10° C. in an ice bath. To this solution 9.4 g (0.25 m) sodium borohydride was added in parts while keeping the temperature below 20° C. It was allowed to stir at 20° C. for 30 minutes and one hour at room temperature. The mixture was poured into 500 ml ice water. The aqueous solution was made alkaline by dropwise addition of 120 ml 50% aqueous sodium hydroxide solution below 25° C. The product was extracted with hexane, (2×100 ml) which was washed with saturated sodium chloride solution, dried on anhydrous magnesium sulfate and evaporated to give a clear liquid. The product was distilled to give a clear colorless liquid product, 21.8 g B.P. 40°/0.5 mm. Yield 71%.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:19]2[CH:28]=[C:27]3[C:22]([CH2:23][CH2:24][CH2:25][N:26]3[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:21][CH:20]=2)=[N:13][C:14]=1[C:15]([O:17][CH3:18])=[O:16])C1C=CC=CC=1>CCOC(C)=O.CCO.C(O)(=O)C.[Pd]>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:19]2[CH:28]=[C:27]3[C:22]([CH2:23][CH2:24][CH2:25][N:26]3[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:21][CH:20]=2)=[N:13][C:14]=1[C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)c1nc(-c2ccc3c(c2)N(C(=O)OC(C)(C)C)CCC3)ccc1OCc1ccccc1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COC(=O)c1nc(-c2ccc3c(c2)N(C(=O)OC(C)(C)C)CCC3)ccc1O
Reaction time: 24 h

Procedure:
To a solution of tert-butyl 7-(5-(benzyloxy)-6-(methoxycarbonyl)pyridin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (29C) (2.72 g, 5.74 mmol) in EtOAc (80 mL) and EtOH (80 mL) and glacial acetic acid (˜30 drops) was added 10% Pd—C (420 mg). The reaction mixture was stirred under an atmosphere of hydrogen for 24 hrs, filtered through a bed of Celite, and concentrated to provide the desired product tert-butyl 7-(5-hydroxy-6-(methoxycarbonyl)pyridin-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (29D): 1H NMR (300 MHz, CDCl3) δ 10.67 (1H, s), 8.30 (1H, d), 7.86 (1H, d), 7.56 (1H, dd), 7.42 (1H, d), 7.15 (1H, d), 4.05 (3H, s), 3.74 (2H, m), 2.80 (2H, t), 1.95 (2H, m), 1.56 (9H, s).
Reaction SMILES: [CH:1]([Mg]Br)=[CH2:2].CN([CH2:8][CH2:9]N(C)C)C.[Si:13]([O:20][C@H:21]([CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])/[CH:22]=[N:23]\[S@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1COCC1>[Si:32]([O:31][CH2:30][C@@H:21]([O:20][Si:13]([C:16]([CH3:19])([CH3:17])[CH3:18])([CH3:15])[CH3:14])[C@@H:22]([NH:23][S@:24]([C:26]([CH3:27])([CH3:28])[CH3:29])=[O:25])[CH:1]=[CH2:2])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34].[Si:32]([O:31][CH2:30][C@@H:21]([O:20][Si:13]([C:16]([CH3:19])([CH3:17])[CH3:18])([CH3:15])[CH3:14])[C@H:22]([NH:23][S@:24]([C:26]([CH3:27])([CH3:28])[CH3:29])=[O:25])[CH:8]=[CH2:9])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34]
Reactant: CC(C)(C)[S@](=O)/N=C\[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Reactant: C=C[Mg]Br
Reactant: CN(C)CCN(C)C
Solvent: C1CCOC1
Product: C=C[C@@H](N[S@@](=O)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Product: C=C[C@H](N[S@@](=O)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 39 %
Yield: 54 %

Procedure:
To a 2.0 L round bottom flask containing vinylmagnesium bromide (92 ml, 92 mmol) was added THF (40 mL) and the mixture was allowed to stir at −78° C. for 5 min. At this time, TMEDA (23 ml, 154 mmol) was added via syringe followed by (S,Z)—N—((S)-2,3-bis(tert-butyldimethylsilyloxy)propylidene)-2-methylpropane-2-sulfinamide (13.0 g, 31 mmol) in THF. The reaction was allowed to stir at −78° C. for 4 h and then allowed to slowly warm to RT overnight. The reaction was quenched by the addition of ammonium chloride (sat, 100 ml). The aqueous layer was extracted with EtOAc, washed with brine, dried sodium sulfate, filtered and concentrated to give a crude oil that was purified by silica gel column to give (S)—N-((2S,3S)-1,2-bis(tert-butyldimethylsilyloxy)pent-4-en-3-yl)-2-methylpropane-2-sulfinamide (5.45 g, 39% yield, higher Rf) and (S)—N-((2S,3R)-1,2-bis(tert-butyldimethylsilyloxy)pent-4-en-3-yl)-2-methylpropane-2-sulfinamide (7.43 g, 54% yield, lower Rf).
Reaction SMILES: [CH2:1]([C:3]1[C:4](CO)=[C:5]([CH3:10])[C:6]([OH:9])=[CH:7][CH:8]=1)[OH:2].[C:13]([O:16][C:17](=[O:19])[CH3:18])(=[O:15])C.[O:20]1CCCC1>>[CH3:3][C:1]([CH2:18][C:17]([OH:16])=[O:19])=[O:2].[CH2:10]([C:5]1[C:6]([OH:9])=[C:7]([CH2:13][OH:15])[CH:8]=[C:3]([CH3:1])[CH:4]=1)[OH:20]
Reactant: CC(=O)OC(C)=O
Reactant: C1CCOC1
Reactant: Cc1c(O)ccc(CO)c1CO
Product: CC(=O)CC(=O)O
Product: Cc1cc(CO)c(O)c(CO)c1

Procedure:
The diacetate of 2,6-dimethylol-p-cresol (DMPC) was prepared by reacting 3.4 g of the dimethylol cresol with 4.8 g of acetic anhydride in the presence of 7.8 g of tetrahydrofuran.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[NH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C(N(CC)CC)C>C(#N)C>[Cl:8][C:4]1[N:3]=[C:2]([NH:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=[N:6][CH:5]=1
Reactant: CCOC(=O)CN
Reactant: Clc1cncc(Cl)n1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)CNc1cncc(Cl)n1
Temperature: 80 °C
Yield: 48.8 %

Procedure:
To 2,6-dichloropyrazine (50 g, 336 mmol) and ethyl 2-aminoacetate (34.6 g, 336 mmol) was added triethylamine (140 mL, 1007 mmol) and acetonitrile (350 mL). The reaction was heated at 80° C. for 3 d. Precipitated triethylamine salts were removed by filtration and washed with ethyl acetate and hexane (1:1) multiple times. The filtrate and wash solvent were combined and concentrated. The resulting white-yellow precipitate was filtered and washed with 20% ethyl acetate in hexane to afford an off-white solid. The filtrate was subjected to the same process to give an additional batch of off-yellow solid. The batches were combined to afford the title compound (35.5 g, 164 mmol, 49% yield). MS (ESI) m/z 216.1 [M+1]+.
Reaction SMILES: [C:1](CC(O)=O)#[N:2].C(O[C:11](=[O:13])[CH3:12])(=O)C.[CH3:14][NH:15][C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:17]>C(O)(=O)C>[NH2:2][C:1]1[N:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16](=[O:17])[N:15]([CH3:14])[C:11](=[O:13])[CH:12]=1
Reactant: CNC(=O)Nc1ccccc1
Reactant: N#CCC(=O)O
Reactant: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: Cn1c(=O)cc(N)n(-c2ccccc2)c1=O

Procedure:
To a solution of 38 g (0.44 mol) of cyanacetic acid, 200 ml of acetic anhydride and 200 ml of acetic acid was added 60 g of 1-methyl-3-phenylurea. The solution was stirred at 90°-100° C. for some hours. After cooling, 65.5 g of 1-cyanoaceto-1-methyl-3-phenylurea (XV) was filtered off (mp 180° C). This was dissolved in 3 1 of boiling ethanol and 10 ml of 10% soda solution was added. After cooling and filtration, the filtrate was evaporated and the crystals were washed with ethanol. Yield 46.7 g (XVI) NMR.