Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:34]=[CH:33][C:27]([O:28]CC(O)=O)=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.Cl.C([O:40][C:41](=[O:45])[C@H:42]([CH3:44])[NH2:43])(C)(C)C.CN1CC[O:50][CH2:49][CH2:48]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(C(F)(F)F)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:34]=[CH:33][C:27]([O:28][CH2:48][C:49]([NH:43][C@H:42]([C:41]([OH:40])=[O:45])[CH3:44])=[O:50])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1
Reactant: CN1CCOCC1
Reactant: C[C@H](N)C(=O)OC(C)(C)C
Reactant: O=C(O)COc1ccc([C@@H]2[C@@H](SCC(=O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: C[C@H](NC(=O)COc1ccc([C@@H]2[C@@H](SCC(=O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1)C(=O)O
Reaction time: 2 h
Yield: 101.2 %

Procedure:
A solution of [4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid (0.020 g, 0.041 mmol), L-Alanine tert-butyl ester hydrochloride (0.009 g, 0.050 mmol) and N-Methylmorpholine (0.018 ml, 0.163 mmol) in DCM (4 ml) was stirred for 5 min. TBTU (0.017 g, 0.053 mmol) was added. The formation of the ester was confirmed after 3 h. M/z: 611.1. TFA (3 ml) was added. After 2 h, the mixture was diluted with toluene (2 ml) and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.023 g (>98%) of the title product was obtained as a white solid. M/z: 555.1. 1H NMR (DMSO, 400 MHz): δ 1.17 (d, 3H), 3.73-3.82 (m, 1H), 4.33 (d, 1H), 4.35 (ABq, 2H), 4.43 (s, 2H), 5.15 (d, 1H), 6.92-7.98 (m, 2H), 7.10-7.24 (m, 4H), 7.29-7.39 (m, 4H), 7.84 (d, 1H), 7.97-8.04 (m, 2H).
Reaction SMILES: [CH3:1][C:2]([C:5]1[C:10]([OH:11])=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[N:8]=[C:7]([NH:16][C:17]([NH2:19])=[S:18])[N:6]=1)([CH3:4])[CH3:3].C([CH:22](Br)[C:23](=O)[C:24]([O-:26])=[O:25])C.[CH3:29][CH2:30]CCCC>C(O)C.O>[CH2:29]([O:26][C:24]([C:23]1[N:19]=[C:17]([NH:16][C:7]2[N:8]=[C:9]([C:12]([CH3:13])([CH3:15])[CH3:14])[C:10]([OH:11])=[C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[N:6]=2)[S:18][CH:22]=1)=[O:25])[CH3:30]
Reactant: CCCCCC
Reactant: CC(C)(C)c1nc(NC(N)=S)nc(C(C)(C)C)c1O
Reactant: CCC(Br)C(=O)C(=O)[O-]
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1csc(Nc2nc(C(C)(C)C)c(O)c(C(C)(C)C)n2)n1

Procedure:
N-[4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]thiourea (1.0 g, 3.5 mmol) is added to a solution of ethylbromopyruvate (0.72 g, 3.7 mmol) in 25 mL of ethanol. The mixture is warmed to reflux for 4.5 hours, then diluted with 100 mL of water. The pH of the solution is adjusted to 4 with saturated NaCHO3. The resulting precipitate is collected by filtration and recrystallized from ethanol/water. Yield of 2-([4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]amino)-4-thiazolecarboxylic acid ethyl ester is 0.86 g (65%). An analytical sample was obtained by treating an aliquot with boiling hexane for 10 minutes; mp 204°-206° C.
Reaction SMILES: O=C(NN[C:13]([N:15]1[CH2:21][C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][C:17]2[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:16]1=2)=[O:14])CCC1C=CC=CN=1.FC(F)(C(O)C1C=CN=CC=1)C(NN)=[O:34].ClC1C=CC2OC3C=CC=CC=3CN(C(Cl)=O)C=2C=1>C(O)(=O)C.Cl>[Cl:30][C:28]1[CH:27]=[CH:26][C:17]2[O:18][C:19]3[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=3[CH2:21][N:15]([C:13]([OH:14])=[O:34])[C:16]=2[CH:29]=1
Reactant: NNC(=O)C(F)(F)C(O)c1ccncc1
Reactant: O=C(CCc1ccccn1)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Agent: Cl
Agent: O=C(Cl)N1Cc2ccccc2Oc2ccc(Cl)cc21
Solvent: CC(=O)O
Product: O=C(O)N1Cc2ccccc2Oc2ccc(Cl)cc21

Procedure:
The free base of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxy-1-oxo-3-(4-1-oxo-3-(4-pyridinyl) propyl]hydrazide (51) was prepared in the same manner as 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-pyridinyl)propyl]hydrazide (6), as described above in Example 6, on a 1.75 mmol scale from α,α-difluoro-β-hydroxy-3-(4-pyridinyl)-propanoic acid, hydrazide (50), prepared in the manner described above in Example 50, and 8-chlorodibenz-[b,f][1,4]oxazepine-10 (10H)-carbonyl chloride (2), prepared in the manner described above in Example 2, for a yield of 0.098 g (12%) of product. The free base was taken up in acetic acid (1.5 mL) and 1M HCl (1.5 mL). The material was lyophilized to yield 0.049 mg of the hydrochloride salt. Analysis calculated for C22H17N4O4F2Cl.HCl.0.25 H2O (M.W. 514.83): C, 51.23; H, 3.62; N, 10.86. Found: C, 50.85; H, 3.67; N, 10.94.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10](=[O:15])[CH2:11][CH2:12][CH:13]=[CH2:14])=[CH:4][N:3]=1.[C:16]([O:24][CH2:25][CH3:26])(=[O:23])[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].CC[O-].[Na+]>CCO>[CH2:21]([O:20][C:18](=[O:19])[CH:17]([C:16]([O:24][CH2:25][CH3:26])=[O:23])[CH:8]([C:5]1[CH:6]=[N:7][C:2]([CH3:1])=[N:3][CH:4]=1)[CH2:9][C:10](=[O:15])[CH2:11][CH2:12][CH:13]=[CH2:14])[CH3:22]
Reactant: C=CCCC(=O)C=Cc1cnc(C)nc1
Reactant: CCOC(=O)CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: C=CCCC(=O)CC(c1cnc(C)nc1)C(C(=O)OCC)C(=O)OCC
Reaction time: 1.5 h

Procedure:
The enone 15-3 (5.73 g, 28.4 mmol) was dissolved in TBF (200 mL) and EtOH (80 mL) at room temperature. To this was added diethyl malonate (6.46 mL, 42.5 mmol) and NaOEt (1 mL, 2.8 mmol) and the mixture stirred for 1.5 hours. The solution was partitioned between saturated NaHCO3 solution and EtOAc, washed with water, brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with EtOAc) to give the diester 15-4 as an oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=2)[C:5]=1[F:18].[C:20](Cl)(=[O:24])[CH:21]([CH3:23])[CH3:22].C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([NH:10][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[CH:7]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=2)[C:5]=1[F:18]
Reactant: CC(C)C(=O)Cl
Reactant: COC(=O)c1cc(N)cc(-c2ccc(C)cn2)c1F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(NC(=O)C(C)C)cc(-c2ccc(C)cn2)c1F
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 109.9 %

Procedure:
5-Amino-2-fluoro-3-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester (560 mg, 1.9 mmol) was dissolved in 20 mL methylene chloride, and the mixture was cooled to 0° C. Isobutyryl chloride (221 mg, 2.1 mmol) and triethylamine (575 mg, 5.7 mmol) were added, and the mixture was stirred at 0° C. for 30 minutes. The reaction mixture was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give 690 mg (99%) of 2-fluoro-5-isobutyrylamino-3-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[C:12]([Br:14])[CH:11]=[C:10]2[C:5]=1[N:6]=[C:7]([O:17][CH3:18])[C:8]([O:15][CH3:16])=[N:9]2.[O:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[C:24](O)=[O:25].Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.C1COCC1>[Br:14][C:12]1[CH:11]=[C:10]2[C:5]([N:6]=[C:7]([O:17][CH3:18])[C:8]([O:15][CH3:16])=[N:9]2)=[C:4]([CH2:3][NH:2][C:24]([C:20]2[O:19][CH:23]=[CH:22][CH:21]=2)=[O:25])[CH:13]=1
Reactant: O=C(O)c1ccco1
Reactant: COc1nc2cc(Br)cc(CN)c2nc1OC
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: C1CCOC1
Product: COc1nc2cc(Br)cc(CNC(=O)c3ccco3)c2nc1OC

Procedure:
300 mg (1 mmol) of 5-aminomethyl-7-bromo-2,3-dimethoxy-quinoxaline hydrochloride, 124 mg (1.1 equiv.) of furan-2-carboxylic acid, 212 mg (1.1 equiv.) of N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride and 12.2 mg (0.1 equiv.) of 4-dimethylamino-pyridine are stirred in dried THF at 20° C. for 20 hours. The mixture is poured onto water, and the solid is filtered off and washed with water and diethyl ether. After drying under a high vacuum, the title compound is obtained in the form of a beige solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH2:10])[CH3:9])=[CH:4][CH:3]=1.Cl[CH2:12][CH2:13][N:14]([CH2:25][CH2:26]Cl)[S:15]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)(=[O:17])=[O:16].CCN(C(C)C)C(C)C>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:26][CH2:25][N:14]([S:15]([C:18]3[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=3)(=[O:17])=[O:16])[CH2:13][CH2:12]2)[CH3:9])=[CH:4][CH:3]=1
Reactant: C[C@H](N)c1ccc(Br)cc1
Reactant: Cc1ccc(S(=O)(=O)N(CCCl)CCCl)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)N2CCN([C@@H](C)c3ccc(Br)cc3)CC2)cc1
Temperature: 125 °C
Reaction time: 20 h
Yield: 76.4 %

Procedure:
A mixture of (S)-1-(4-bromophenyl)ethanamine (0.36 ml, 2.50 mmol) and N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide (864 mg, 2.62 mmol) in DIPEA (0.873 ml, 5.0 mmol) was heated at 125° C. and stirred for 20 h. The reaction mixture was cooled to RT then diluted into DCM (30 ml) and washed with Na2CO3 2M in water (40 ml). The aqueous phase was further extracted with DCM (3×20 ml) and the combined organic fractions were dried over Na2SO4, filtered and evaporated to dryness. AcOEt was added in small portions into a hot mixture of the crude in heptane until complete dissolution. The mixture was allowed to cooled to RT during which time precipitation occurred. The mixture was cooled to 0° C. (ice bath) for 30 min then filtered. The solid was washed with heptane, dried under air and finally under high vacuum to yield the title compound (810 mg, 1.91 mmol, 77% yield) as a brownish solid. HPLC: AtRet=1.66 min; LC-MS: m/z 425.4 [M+H]+; 1H NMR (400 MHz, CDCl3): 1.29 (d, J=6.8, 3H), 2.41-2.50 (m, 5H), 2.52-2.61 (m, 2H), 2.93-3.05 (m, 4H), 3.34 (q, J=6.7, 1H), 7.09-7.16 (m, 2H), 7.31-7.37 (m, 2H), 7.39-7.44 (m, 2H), 7.61-7.66 (m, 2H).
Reaction SMILES: O[C:2]1([C:14]([CH:15](O)[CH2:16][CH2:17][CH2:18][CH3:19])=[CH:13][CH:12]=[CH:11][CH2:10]1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[Cl:36]([O-:40])(=[O:39])(=[O:38])=[O:37].[Na+]>C1C=CC=CC=1>[Cl:36]([O-:40])(=[O:39])(=[O:38])=[O:37].[CH2:16]([C:15]1[N+:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]2[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=12)[CH2:17][CH2:18][CH3:19]
Reactant: CCCCC(O)C1=CC=CCC1(O)Cc1ccccn1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [Na+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: c1ccccc1
Product: CCCCc1c2ccccc2cc2cccc[n+]12
Yield: 11 %

Procedure:
To a refluxing solution of 11.1 g (0.04 mol) of 2-[1-hydroxy-6'-(1-hydroxypentyl)-benzyl]pyridine in 250 mL of benzene was added 23.9 mL (0.14 mol) of triflic anhydride in 5 min, the mixture was heated for 65 min and then cooled. The reaction mixture was concentrated in vacuo, the residual oil was triturated in ether and decanted. The oil was chromatographed on silica (ethyl acetate/methylene chloride, 1:1) to afford an oil, which was treated with sodium perchlorate solution. The salt was triturated in hot water, decanted, and the residue crystallized on cooling. The above solid was crystallized (2x) from ethyl acetate/methylene chloride to afford 1.5 g (11%) of 6-butylbenzo[b]quinolizinium perchlorate (Formula II: R1 =R7 =H;R2 =n-butyl;X- =ClO4-), as a pale solid, m.p. 174°-177° C.
Reaction SMILES: C([O:5][C:6](=[O:33])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)=[CH:22][N:21]=2)=O)[N:15]=1)([CH3:9])[CH3:8])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[ClH:32].[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][CH2:17][CH2:16][C:14]3[N:15]=[C:11]([S:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:33])=[O:5])[S:12][CH:13]=3)=[N:21][CH:22]=2)=[CH:27][CH:28]=1
Reactant: CC(C)(C)OC(=O)C(C)(C)Sc1nc(CC(=O)Nc2ccc(-c3ccc(Cl)cc3)cn2)cs1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(Sc1nc(CCNc2ccc(-c3ccc(Cl)cc3)cn2)cs1)C(=O)O
Product: Cl
Temperature: 25 °C
Reaction time: 20 h
Yield: 102 %

Procedure:
2-{[4-(2-{[5-(4-Chlorophenyl)pyridin-2-yl]amino}-2-oxoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (145 mg) obtained in Example 242-3 was dissolved in dichloromethane (2 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for 20 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; chloroform:methanol=20:1). The obtained compound was dissolved in diethyl ether (4 mL), 4 mol/L hydrochloric acid-ethyl acetate (0.5 mL) was added, and the mixture was stirred at room temperature for 1 hr. The precipitated solid was collected by filtration to give the title compound (69 mg) as a white solid.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].CC(O)C.[CH2:17]([NH2:33])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>O>[CH2:17]([NH:33][CH:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: CCCCCCCCCCCCCCCCN
Solvent: CC(C)O
Solvent: O
Product: CCCCCCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reaction time: 8 h

Procedure:
A 2 L two neck round bottom flask equipped with condenser was charged with D(+) glucose (60 g, 0.333 moles), 2-propanol (900 mL), hexadecylamine (81 g, 0.334 moles) and deionized water (300 mL). The reaction was stirred and heated to 50°-55° celsius for 1 hour to obtain a homogeneous solution. The reaction was then allowed to run overnight at room temperature. The reaction precipitated out after 2-3 hours.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[C:17]2[C:16](=[O:18])[N:15]([CH3:19])[CH2:14][C:13]=2[C:12]([C:20]([OH:22])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.CN(C=O)C>[CH3:19][N:15]1[C:16](=[O:18])[C:17]2[C:13](=[C:12]([C:20]([N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[O:22])[CH:11]=[CH:10][C:9]=2[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:14]1
Reactant: C1CCNC1
Reactant: CN1Cc2c(C(=O)O)ccc(NC(=O)OC(C)(C)C)c2C1=O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1Cc2c(C(=O)N3CCCC3)ccc(NC(=O)OC(C)(C)C)c2C1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
7-[(Tert-butoxycarbonyl)amino]-2-methyl-1-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid (Compound 116C, 45 mg, 0.15 mmol), pyrrolidine (123 uL, 1.47 mmol), TBTU (236 mg, 0.734 mmol), DIPEA (128 uL, 0.734 mmol) and DMF (1 mL) were mixed and stirred at room temperature for 2 hours. The reaction mixture was diluted with EtOAc and washed with water (2×) and brine. The crude product was purified by column chromatography. MS (ES+): m/z 360.34 (100) [MH+]; HPLC: tR=1.20 min (UPLC, Analytical).
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])(C)(C)C.[C:19]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:23][C:22](C(Cl)=O)=[CH:21][CH:20]=1.[NH2:34][CH:35]([CH3:38])[CH2:36][OH:37]>>[C:28]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:29]=[CH:30][C:31]([C:6]([N:8]2[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]2[C:16]([NH:34][CH:35]([CH3:38])[CH2:36][OH:37])=[O:18])=[O:7])=[CH:32][CH:33]=1
Reactant: CC(N)CO
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Reactant: CON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Product: CON=C1C[C@@H](C(=O)NC(C)CO)N(C(=O)c2ccc(-c3ccccc3)cc2)C1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, [1,1′-biphenyl]-4-carbonyl chloride, and (2RS)-2-amino-1-propanol, the title compound was obtained in 81% purity by HPLC. MS(ESI+): m/z=396.
Reaction SMILES: BrC[CH2:3][CH2:4][CH2:5][C:6]([CH3:21])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:7][O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1.[Br:22]CCCC(C)(C1C=CC=CC=1)CO.O1C=CCCC1>C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:22][CH2:3][CH2:4][CH2:5][C:6]([CH3:21])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:7][O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1
Reactant: CC(CCCCBr)(COC1CCCCO1)c1ccccc1
Reactant: CC(CO)(CCCBr)c1ccccc1
Agent: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: CC(CCCBr)(COC1CCCCO1)c1ccccc1
Yield: 95 %

Procedure:
According to the method described for the synthesis of 207d, 206b (20.0 g, 77.8 mmol) was treated with 3,4-dihydro-2H-pyran (8.2 g, 96.5 mmol) and p-toluenesulfonic acid hydrate (0.57 g, 3.0 mmol) in CH2Cl2 (350 mL) to afford 207b (25.2 g, 95%) as an oil, which was used without further purification. 1H NMR (CDCl3): 7.26-7.08 (m, 5H), 4.45 (m, 1H), 3.72 (m, 1H), 3.58 (m, 1H), 3.35-3.05 (m, 2H), 3.28 (t, 2H, J=6.6), 1.95-1.39 (m, 10H), 1.25 (s, 3H). 13C NMR (CDCl3): δ 145.38, 128.15, 126.51, 126.03, 99.06, 98.92, 76.20, 61.91, 61.80, 41.82, 41.74, 37.58, 37.43, 34.65, 30.61, 27.88, 25.58, 23.03, 22.90, 19.39, 19.32. HRMS (LSIMS, nba): Calcd for C17H26O2Br (MH+): 341.1116, found: 341.1127.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:22])=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH3:13])[N:8]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].[CH2:29]([CH:31]1[O:33][CH2:32]1)Br>CC(C)=O>[Br:1][C:2]1[C:3]([O:22][CH2:29][CH:31]2[CH2:32][O:33]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:17])[CH3:13])[N:8]=[CH:7]2
Reactant: BrCC1CO1
Reactant: CC(Cn1ncc2ccc(O)c(Br)c21)O[Si](C)(C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(Cn1ncc2ccc(OCC3CO3)c(Br)c21)O[Si](C)(C)C(C)(C)C
Yield: 73.6 %

Procedure:
A suspension of the product from Step C (4.47 g, 11.6 mmol), potassium carbonate (2.25 g, 16 mmol), and epibromohydrine (1.59 mL, 19 mmol) in acetone (230 mL) was heated at reflux for 20 h. Additional epibromohydrine (1.5 mL, 17.9 mmol) was added and the mixture heated at reflux for 18 h. The solid was removed by filtration and the filtrate was concentrated to an oil which was dissolved in EtOAc (150 mL). This solution was washed with saturated aqueous ammonium acetate (150 mL), dried (MgSO4), is and evaporated to a residue which was purified by chromatography (silica, 2% to 10% EtOAc/hexane) to afford an oil (3.77 g, 74%): LC/MS (+APCI) m/z 441, 443 (M+H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([O:22][CH2:23][C:24]([O:26]C)=[O:25])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][C:14]=2[C:28](=[O:30])[NH2:29].[OH-].[Na+]>C(O)C>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([O:22][CH2:23][C:24]([OH:26])=[O:25])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][C:14]=2[C:28](=[O:30])[NH2:29]
Reactant: COC(=O)COc1cccc2c1c1c(C(N)=O)cccc1n2Cc1ccccc1C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1ccccc1Cn1c2cccc(OCC(=O)O)c2c2c(C(N)=O)cccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.8 %

Procedure:
A suspension of the {9-[(2-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester (15.5 mg, 0.039 mM) and 0.04 mL (0.04 mM) of 1 N NaOH in 5 mL of ethanol was stirred for 24 hours at 25° C. The resultant white precipitate was collected by filtration, washed with a small amount of EtOH, then dried in vacuo to afford 10 mg (63%) of the {9-[(2-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt as a whitw powder. 1H NMR (DMSO-d6) δ7.55 (br s, 1H), 7.5-7.0 (m, 7H), 6.9 (d, 1H, J=8 Hz), 6.85 (t, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.2 (d, 1H, J=8 Hz), 5.6 (s, 2H), 4.35 (s, 2H), and 2.5 (s, 3H). IR (KBr, cm−1) 3390, 1656, 1613, 1595, 1573, 1498, 1455, 1408, 1325, 1332, and 719. MS (ES) m/e 387, 389.
Reaction SMILES: [O:1]1[C@H:8]([CH2:9][OH:10])[C@H:6]([OH:7])[C@H:4]([OH:5])[CH:3]=[CH:2]1.[C:11](OC=C)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O>[C:11]([O:10][CH2:9][C@H:8]1[O:1][CH:2]=[CH:3][C@@H:4]([OH:5])[C@H:6]1[OH:7])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C=COC(=O)c1ccccc1
Reactant: OC[C@H]1OC=C[C@@H](O)[C@H]1O
Solvent: O
Product: O=C(OC[C@H]1OC=C[C@@H](O)[C@H]1O)c1ccccc1

Procedure:
1.0 g (6.85 mmol) of galactal is taken up in 0.5-1.5 ml of H2O, 8 g of crushed molecular sieves are added, and the mixture is stirred with 1 g of Candida lipase AY-20 (Meito, Sangyo) or 1 g of lipase P (Amano) in 10-15 ml of vinyl benzoate at room temperature for 8-10 h. Filtering off the enzyme, concentration of the solution in vacuo, taking up the residue in ethyl acetate and extracting it with aqueous NaHCO3 solution, and subsequent chromatography on silica gel (ethyl acetate/hexane 1:1) result in 65-68% (about 1130 mg) of the desired 6-O-benzoylgalactal.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][CH2:13][CH:14]([CH3:26])[C:15]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[Cl:25])=[O:16].CCN(CC)CC>C(Cl)Cl>[Cl:25][C:18]1[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:17]=1[C:15](=[O:16])[CH:14]([CH3:26])[CH2:13][CH:12]=[O:11]
Reactant: COc1ccc(C(=O)C(C)CCO)c(Cl)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)C(C)CC=O)c(Cl)c1
Temperature: -68 °C
Reaction time: 0.25 h

Procedure:
To a 500 mL, 3-neck round bottom flask, equipped with a mechanical stirrer and an internal thermometer, was added DMSO (17.0 mL, 239 mmol) and CH2Cl2 (200 mL). The solution was cooled to −68° C. with a dry ice/acetone bath. To this solution was added oxalyl chloride (10.4 mL, 119 mmol) slowly. The mixture was stirred at −68° C. for 15 min followed by the addition of a solution of 4-hydroxy-1-(2-chloro-4-methoxyphenyl)-2-methylbutan-1-one (12.9 g, 53.0 mmol) in CH2Cl2 (20.0 mL) slowly. After stirring at <−68° C. for 1 h, to the mixture was added Et3N (70.0 mL, 502 mmol). The cooling bath was removed after 5 min and the mixture was stirred at room temperature for 1.5 h. The mixture was diluted with water (200 mL). The aqueous layer was extracted with CH2Cl2 (2×). The combined organic solutions was concentrated in vacuo to dryness and the residue was subjected to column chromatography (silica gel, 1/10 EtOAc/heptane) to give 8.07 g (63%) of light yellow oil as the title compound:
Reaction SMILES: [C:1]([OH:32])(=[O:31])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].CO.[CH2:35](O)[CH3:36]>>[CH2:35]([O:31][C:1](=[O:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH3:36]
Reactant: CCO
Reactant: CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)OCC
Reaction time: 0.75 h

Procedure:
The acid chloride of 1-triacontanoic acid is converted to the ester by adding methanol or ethanol and stirring for 1/2 to 1 hour. The alcohol was evaporated on a rotary evaporator leaving ethyl-1-triacontanoate. The ester is then reacted in a pressure vessel under about 250 atmospheres of hydrogen in the presence of a powdered copper chromite catalyst for about 12 hours at 250° C. to produce 1-triacontanol. One part of catalyst is present for every 5 to 10 parts of ester.