Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:10]([OH:13])([CH3:12])[CH3:11])[CH:7]=[N:8][CH:9]=1.I[CH3:15]>CN(C=O)C>[Br:3][C:4]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]([O:13][CH3:15])([CH3:11])[CH3:12])[CH:5]=1
Reactant: CI
Reactant: CC(C)(O)c1cncc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(C)(C)c1cncc(Br)c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 69.8 %

Procedure:
To a mixture of NaH (240 mg, 6.02 mmol) in DMF (dry, 4 mL) at 0° C. is added the solution of 2-(5-bromo-pyridin-3-yl)-propan-2-ol (500 mg, 2.31 mmol) in DMF (dry, 4 mL). The mixture is stirred at 0° C. for 15 min then raised to room temperature and stirred for 1 h. The mixture is then cooled back to 0° C. and iodomethane (397 mg, 2.80 mmol) iss added. The reaction mixture is stirred at room temperature overnight and is quenched by adding water dropwise. The mixture is partitioned between DCM and water. The DCM phase is separated and then washed with water twice. The DCM phase is evaporated under high vacuum. The residue is separated by silica gel flash column (EtOAc/Hepane 0 to 40% gradient, then 40%) to obtain 371 mg 3-bromo-5-(1-methoxy-1-methyl-ethyl)pyridine.
Reaction SMILES: [C:1]1([C:5]([OH:7])=[O:6])[CH2:4][CH2:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[F:14][C:15]1[C:20]([F:21])=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:16]=1O.C(N(CC)CC)C.C1(C(Cl)=O)CCC=1>C(Cl)Cl>[C:1]1([C:5]([O:7][C:16]2[C:17]([F:24])=[C:18]([F:23])[C:19]([F:22])=[C:20]([F:21])[C:15]=2[F:14])=[O:6])[CH2:4][CH2:3][CH:2]=1
Reactant: O=C(O)C1=CCC1
Reactant: Oc1c(F)c(F)c(F)c(F)c1F
Agent: O=C(Cl)C(=O)Cl
Agent: O=C(Cl)C1=CCC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C1=CCC1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 43.8 %

Procedure:
Cyclobut-1-enecarboxylic acid (0.51 mmol, 50 mg) was dissolved in 0.5 ml dry CH2Cl2. The solution was cooled to 0° C. and oxalyl dichloride (0.51 mmol, 43 μl) was added. The temperature of the solution was raised to room temperature, and the mixture was allowed to react for 1 h. The solvent was evaporated to generate a viscous oil. 2,3,4,5,6-Pentafluorophenol (0.51 mmol, 94 mg) and triethylamine (1.02 mmol, 142 μl) were dissolved in 0.5 ml dry CH2Cl2, and the solution was stirred at 0° C. for 45 min before being added to a vial containing cyclobut-1-enecarboxylic chloride. The reaction mixture was stirred for 16 h at rt. The reaction was quenched with 1 N HCl, and was extracted with CH2Cl2 (30 ml). The CH2Cl2 solution was washed with 5% NaHCO3 (2×10 ml), dried over Na2SO4, concentrated by rotary evaporation, and then purified by flash column chromatography (100% CH2Cl2) to yield 13 as a colorless oil (59 mg, 44%). 1H-NMR (500 MHz, CDCl3) δ 7.12 (s, 1H), 2.86 (m, 2H), 2.60 (m, 2H). 13C-NMR (125 MHz, CDCl3) δ 156.7, 152.6, 142.1, 140.3, 138.8, 138.3, 135.2, 53.3, 30.6, 29.2. HRMS (ESI) calcd. for C11H6O2F5 [M+H]+ 265.0293, found 265.0288.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:16][CH:13]([CH:14]=[CH2:15])[CH:4]([CH:5]([O:9][CH2:10][O:11][CH3:12])[CH2:6][C:7]#N)[O:3]1.[H-].C([Al+]C(C)C)(C)C.S(=O)(=O)(O)[OH:27]>C1(C)C=CC=CC=1.C(OCC)C>[CH3:1][C:2]1([CH3:17])[O:16][CH:13]([CH:14]=[CH2:15])[CH:4]([CH:5]([O:9][CH2:10][O:11][CH3:12])[CH2:6][CH:7]=[O:27])[O:3]1
Reactant: C=CC1OC(C)(C)OC1C(CC#N)OCOC
Reactant: O=S(=O)(O)O
Agent: CC(C)[Al+]C(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: C=CC1OC(C)(C)OC1C(CC=O)OCOC
Temperature: -40 °C
Reaction time: 0.5 h

Procedure:
4,5-(Dimethylmethylenedioxy)-3-methoxymethoxy-6-heptenenitrile (159.8 mg) was dissolved in dry toluene, and 1.6 ml of 0.5N diisopropyl aluminum hydride was added at -78° C. The reaction mixture was stirred at -78° C. for 2 hours and at -40° C. for 30 minutes, and 5% dilute sulfuric acid was gradually added at 0° C. The reaction mixture was diluted with diethyl ether, and the organic layer was washed with a sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, concentrated under reduced pressure to afford 91.1 mg of 4,5-(dimethylmethylenedioxy)-3-methoxymethoxy-6-heptenal.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.F[C:10]1[CH:17]=[CH:16][C:15]([CH:18]=[O:19])=[CH:14][C:11]=1[C:12]#[N:13]>>[CH:18]([C:15]1[CH:16]=[CH:17][C:10]([O:8][C:5]2[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=2)=[C:11]([CH:14]=1)[C:12]#[N:13])=[O:19]
Reactant: N#Cc1cc(C=O)ccc1F
Reactant: Cc1ccc(O)cn1
Product: Cc1ccc(Oc2ccc(C=O)cc2C#N)cn1

Procedure:
The title compound was prepared by a procedure similar to that described for D4 starting from 6-methyl-3-pyridinol and 2-fluoro-5-formylbenzonitrile.
Reaction SMILES: [CH:1]([C:3]1[N:10]2[C:6]([S:7][C:8]([C:11]3[C@H:12]([CH3:35])[C@@H:13]4[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]4[C:15]=3[C:16]([O:18]CC3C=CC([N+]([O-])=O)=CC=3)=[O:17])=[CH:9]2)=[CH:5][N:4]=1)=[O:2].F[C:37](F)(F)S(OC)(=O)=O>ClCCl>[CH:1]([C:3]1[N:4]([CH3:37])[CH:5]=[C:6]2[N+:10]=1[CH:9]=[C:8]([C:11]1[C@H:12]([CH3:35])[C@@H:13]3[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]3[C:15]=1[C:16]([O-:18])=[O:17])[S:7]2)=[O:2]
Reactant: COS(=O)(=O)C(F)(F)F
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4c(C=O)ncc4s3)[C@H](C)[C@H]12
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(c3c[n+]4c(C=O)n(C)cc4s3)[C@H](C)[C@H]12
Reaction time: 5 h

Procedure:
To a suspension of 33 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-formylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in 1 ml of dichloromethane was added 0.017 ml of methyl trifluoromethanesulfonate under ice-cooling. The mixture was stirred for 5 hours, and concentrated under reduced pressure. The residual concentrate was dissolved in 2 ml of THF and 2 ml of 1/15 M sodium phosphate buffer (pH 6.6), and 47 mg of 10% Pd-C was added therto. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 2 hours. The catalyst was collected by filtration on Celite, and washed with water. The filtrate was washed with ethyl acetate, and the aqueous layer was purified by column chromatography on DIAION HP-20 (20% methanol in water) and on COSMOSEAL 40C18-PREP (water:methanol=10:1) to give 2.5 mg of the title compound.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:20]=1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.[NH2:33][C:34]1[CH:48]=[CH:47][C:37]([C:38]([NH:40][CH2:41][CH2:42][CH2:43][N:44]([CH3:46])[CH3:45])=[O:39])=[CH:36][CH:35]=1>C(O)(C)C>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:33][C:34]4[CH:48]=[CH:47][C:37]([C:38]([NH:40][CH2:41][CH2:42][CH2:43][N:44]([CH3:45])[CH3:46])=[O:39])=[CH:36][CH:35]=4)=[N:20][C:6]2=3)[CH2:19][CH2:18][CH2:17]1
Reactant: CN(C)CCCNC(=O)c1ccc(N)cc1
Reactant: CN1C(=O)C(F)(F)CN(C2CCC2)c2nc(Cl)ncc21
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: O
Solvent: CC(C)O
Product: CN(C)CCCNC(=O)c1ccc(Nc2ncc3c(n2)N(C2CCC2)CC(F)(F)C(=O)N3C)cc1
Yield: 87.5 %

Procedure:
A mixture of 0.0673 g (0.22 mmole) 2-chloro-9-cyclobutyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-1), 0.0634 g (0.33 mmole) of toluenesulfonic acid monohydrate, 0.0492 g (0.22 mmole) of 4-amino-N-(3-dimethylamino-propyl)-benzamide and 1 mL of isopropanol was heated in a sealed vessel at 140 degrees for 22 hours, cooled and concentrated under reduced pressure. The residue taken up in ethyl acetate and washed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with acetonitrile-methanol-triethylamine (85:15:1) to give 0.0938 g of 4-(9-cyclobutyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-benzamide (I-19)
Reaction SMILES: CO[C:3]([CH:5]1[C:14](=O)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[S:7][CH2:6]1)=[O:4].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][NH2:24])=[CH:19][CH:18]=1>C(O)(=O)C>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:3](=[O:4])[C:5]3[CH2:6][S:7][C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=4[C:14]=3[NH:24]2)=[CH:19][CH:18]=1
Reactant: COC(=O)C1CSc2ccccc2C1=O
Reactant: NNc1ccc(Cl)cc1
Solvent: CC(=O)O
Product: O=c1c2c([nH]n1-c1ccc(Cl)cc1)-c1ccccc1SC2
Temperature: 115 °C
Reaction time: 0.33 h

Procedure:
4Oxo-3-thiochromancarboxylic acid methyl ester (10.4 g., 0.047 mole), [prepared by the method of Moriwake, J. Med. Chem. 9, 163 (1966)], was added to a round bottom flask containing p-chlorophenylhydrazine (7.4 g., 0.052 mole) and 3 ml. of glacial acetic acid. After stirring to obtain a homogeneous mixture, the reaction mixture was heated under nitrogen at an oil bath temperature of 115° C. The reaction mixture quickly liquefied and then turned to a yellow solid. Heating was continued at 115° C. for 20 minutes and the temperature then gradually raised to 180° C. and maintained there for about an hour. The reaction mixture was then cooled to room temperature, the solid was collected by filtration, washed with ether and dried. Recrystallization from isopropanol afforded product, m.p. 235° to 237° C. Weight: 10.3 g (70%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18](F)[N:17]=2)=[N:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([NH2:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[CH:23]1([CH2:29][NH2:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>CS(C)=O>[Cl:1][C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH:30][CH2:29][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[N:17]=2)=[N:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([NH2:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1
Reactant: N[C@H]1CC[C@H](Nc2ncc(Cl)c(-c3cccc(F)n3)n2)CC1
Reactant: NCC1CCCCC1
Solvent: CS(C)=O
Product: N[C@H]1CC[C@H](Nc2ncc(Cl)c(-c3cccc(NCC4CCCCC4)n3)n2)CC1
Temperature: 105 °C
Reaction time: 24 h

Procedure:
A mixture of trans-N1-(5-chloro-4-(6-fluoropyridin-2-yl)pyrimidin-2-yl)cyclohexane-1,4-diamine (12 mg, 0.037 mmol), cyclohexylmethanamine (42.2 mg, 0.373 mmol), and DMSO (0.35 ml) was stirred at about 105° C. for about 24 hours. The excess cyclohexylmethanamine was removed under vacuum to yield a residue. The residue was mixed with 0.5 ml DMSO, filtered, purified by prep HPLC and then lyophilized to yield 9.4 mg of the title compound as a TFA salt. LCMS (m/z): 415.3 (MH+), retention time=0.67 min.; 1H NMR (400 MHz, METHANOL-d4, 45° C.) δ ppm 0.89-1.07 (m, 2 H) 1.10-1.30 (m, 3 H) 1.30-1.54 (m, 4 H) 1.55-1.65 (m, 2 H) 1.69 (d, J=12.91 Hz, 2 H) 1.76 (d, J=12.91 Hz, 2 H) 1.96-2.14 (m, 4 H) 2.98-3.10 (m, 1 H) 3.18 (d, J=6.65 Hz, 2 H) 3.71-3.82 (m, 1 H) 7.03 (d, J=9.00 Hz, 1 H) 7.49 (br. s., 1 H) 7.83 (t, J=8.22 Hz, 1 H) 8.35 (s, 1 H)
Reaction SMILES: [I:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][N:16]3[C:20]([CH3:22])([CH3:21])[C:19](=[O:23])[NH:18][C:17]3=[O:24])[N:8]=2)=[CH:4][CH:3]=1.C1(S([O-])=O)C=CC=CC=1.[Na+].C[C:36]1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)O[C:38]2[C:39](P(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:40][CH:41]=[CH:42][C:37]1=2.C(=O)([O-])[O-].[Cs+].[Cs+].C(O[K])(C)(C)C>[Cl-].C([N+](CCCC)(CCCC)CCCC)C1C=CC=CC=1.CC(O)(C)C.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:36]([N:18]1[C:19](=[O:23])[C:20]([CH3:22])([CH3:21])[N:16]([CH2:15][CH2:14][NH:13][C:9]2[N:8]=[C:7]([C:5]3[S:6][C:2]([I:1])=[CH:3][CH:4]=3)[CH:12]=[CH:11][N:10]=2)[C:17]1=[O:24])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Reactant: CC1(C)C(=O)NC(=O)N1CCNc1nccc(-c2ccc(I)s2)n1
Agent: [Pd]
Agent: CC(C)(C)O[K]
Agent: CCCC[N+](CCCC)(CCCC)Cc1ccccc1
Solvent: CC(C)(C)O
Solvent: Cc1ccccc1
Product: CC1(C)C(=O)N(Cc2ccccc2)C(=O)N1CCNc1nccc(-c2ccc(I)s2)n1
Temperature: 110 °C

Procedure:
A suspension of 50 mg (0.11 mmol) of 1-{2-[4-(5-iodothiophen-2-yl)pyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione, 22 mg (0.13 mmol) of sodium benzenesulfinate, 3 mg (0.0027 mmol) of Pd2 dba3, 3.5 mg (0.00547 mmol) of Xantphos, 71 mg (0.22 mmol) of cesium carbonate, 34 mg (0.109 mmol) of N-benzyl-tri-n-butylammonium chloride and 0.22 mL of a 1 M solution of tBuOK in tBuOH in 3 mL of toluene was heated to 110° C. in a microwave for 10 min. The toluene was removed in vacuo and the residue purified by C-8 prep HPLC to deliver the title compound. MS (M+H)+ 548.
Reaction SMILES: [NH2:1][C:2]1[N:29]([CH2:30][C:31]([OH:34])([CH3:33])[CH3:32])[C:6]2[N:7]=[C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([CH:18]4[CH2:23][CH2:22][N:21]([CH:24]5[CH2:26][CH2:25]5)[CH2:20][CH2:19]4)=[CH:14][C:13]=3[O:27][CH3:28])[N:9]=[CH:10][C:5]=2[C:4](=[O:35])[C:3]=1[C:36]([NH2:38])=[O:37].CC[Cl:41]>C(Cl)Cl.CCOCC>[ClH:41].[NH2:1][C:2]1[N:29]([CH2:30][C:31]([OH:34])([CH3:33])[CH3:32])[C:6]2[N:7]=[C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([CH:18]4[CH2:19][CH2:20][N:21]([CH:24]5[CH2:25][CH2:26]5)[CH2:22][CH2:23]4)=[CH:14][C:13]=3[O:27][CH3:28])[N:9]=[CH:10][C:5]=2[C:4](=[O:35])[C:3]=1[C:36]([NH2:38])=[O:37]
Reactant: CCCl
Agent: COc1cc(C2CCN(C3CC3)CC2)ccc1Nc1ncc2c(=O)c(C(N)=O)c(N)n(CC(C)(C)O)c2n1
Solvent: CCOCC
Solvent: ClCCl
Product: Cl
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a suspension of 0.137 g (0.26 mmol) of the product prepared in step 21.1 in 5 mL of CH2Cl2 are added 1.05 mL (1.05 mmol) of 1.0 M hydrochloric ether. The mixture is stirred for 5 minutes at room temperature and then diluted with ether. The precipitate is drained by suction, rinsed with ether and with pentane, and dried under vacuum. 0.12 g of the expected product is obtained in the form of a yellow solid. Yield (dihydrochloride)=77%. m.p.=206°C. (decomposition). M+H+=568
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:22][CH3:23])=[C:7]([CH:21]=1)[O:8][CH2:9][C:10]1[N:11]=[C:12]([C:16]2[O:17][CH:18]=[CH:19][CH:20]=2)[O:13][C:14]=1[CH3:15].[CH2:24]([N:31]1[CH:35]=[C:34]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:33]([OH:41])=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:24]([N:31]1[CH:35]=[C:34]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:33]([O:41][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([O:22][CH3:23])=[C:7]([O:8][CH2:9][C:10]3[N:11]=[C:12]([C:16]4[O:17][CH:18]=[CH:19][CH:20]=4)[O:13][C:14]=3[CH3:15])[CH:21]=2)=[N:32]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CCOC(=O)c1cn(Cc2ccccc2)nc1O
Reactant: COc1ccc(CCl)cc1OCc1nc(-c2ccco2)oc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cn(Cc2ccccc2)nc1OCc1ccc(OC)c(OCc2nc(-c3ccco3)oc2C)c1
Temperature: 90 °C
Reaction time: 15 h
Yield: 75.8 %

Procedure:
A mixture of 4-(5-chloromethyl-2-methoxyphenoxy)methyl-2-(2-furyl)-5-methyl-1,3-oxazole (2.24 g), ethyl 1-benzyl-3-hydroxy-1H-pyrazole-4-carboxylate (1.50 g), potassium carbonate (0.84 g) and N,N-dimethylformamide (50 mL) was stirred at 90° C. for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:1, v/v) to give ethyl 1-benzyl-3-[(3-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-4-methoxybenzyl)oxy]-1H-pyrazole-4-carboxylate (2.51 g, yield 76%) as colorless crystals. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 147-148° C.
Reaction SMILES: ClCCCC(OC(=O)C)CCCCC.ClCCCC(OC(=O)C)CCCCCCC.C([O:34][CH:35]([CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]CC)[CH2:36][CH2:37][CH2:38][N:39]([CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][C:50]([O:52]CC)=[O:51])[S:40]([CH3:43])(=[O:42])=[O:41])(=O)C>>[OH:34][C@H:35]([CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])[C:36]#[C:37][CH2:38][N:39]([CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][C:50]([OH:52])=[O:51])[S:40]([CH3:43])(=[O:41])=[O:42]
Reactant: CCCCCCCC(CCCN(CCCCCCC(=O)OCC)S(C)(=O)=O)OC(C)=O
Agent: CCCCCC(CCCCl)OC(C)=O
Agent: CCCCCCCC(CCCCl)OC(C)=O
Product: CCCCC[C@@H](O)C#CCN(CCCCCCC(=O)O)S(C)(=O)=O

Procedure:
The synthesis of this compound is carried out as described in Example 1 except that, in Step A, the 1-chloro-4-acetoxynonane is replaced by an equimolar amount of 1-chloro-4-acetoxyundecane (Example C, Step 3). The product of Step A is thus ethyl 7-[N-(4-acetoxyundecanyl)methanesulfonamido]heptanoate. The subsequent step yields 7-[N-(4-hydroxyundecanyl)methanesulfonamido]heptanoic acid (B).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=[O:12].[BH4-].[Na+].Cl>C(O)C>[OH:12][CH2:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1
Reactant: O=Cc1ccc2ccccc2n1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OCc1ccc2ccccc2n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 87.2 %

Procedure:
A solution of 3.0 g of quinoline-2-carboxaldehyde in 100 ml of ethanol was treated with 750 mg of sodium borohydride and stirred at ambient temperature for 15 min. The resulting solution was neutralized with 1N HCl, concentrated in vacuo, and extracted three times with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated to provide 2.65 g (88%) of the crude desired compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7](O)=O.[C:12]1([CH:18]([CH3:20])[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH2:7][C:15]2[CH:16]=[CH:17][C:12]([CH:18]([CH3:20])[CH3:19])=[CH:13][CH:14]=2)[CH:10]=1
Reactant: O=C(O)c1cc(Br)ccc1Cl
Reactant: CC(C)c1ccccc1
Product: CC(C)c1ccc(Cc2cc(Br)ccc2Cl)cc1

Procedure:
Synthesis was performed by a similar method as in Preparation Example 14 using 5-bromo-2-chlorobenzoic acid and cumene.
Reaction SMILES: O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:13][S:14]([C:17]1[CH:18]=[N:19][CH:20]=[C:21]([C:23]#[C:24][C:25](OCC)([O:29]CC)[O:26][CH2:27][CH3:28])[CH:22]=1)(=[O:16])=[O:15]>C1(C)C=CC=CC=1>[CH2:27]([O:26][C:25](=[O:29])[C:24]#[C:23][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([S:14]([CH3:13])(=[O:15])=[O:16])[CH:22]=1)[CH3:28]
Reactant: CCOC(C#Cc1cncc(S(C)(=O)=O)c1)(OCC)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)C#Cc1cncc(S(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 58.7 %

Procedure:
p-Toluenesulfonic acid monohydrate (1.39 g, 0.73 mmol) was added to a solution of 3-methanesulfonyl-5-triethoxyprop-1-ynyl-pyridine (1.20 g, 3.70 mmol) in toluene (40 mL). After stirring overnight at room temperature, the solvent was removed under reduced pressure. The crude product was chromatographed on silica (30% ethyl acetate/hexanes) to give the title compound (0.55 g, 53% yield) as a white solid. 1H NMR (CDCl3) δ 9.17 (d, 1H, J=2.4 Hz), 9.03 (d, 1H J=2.0), 8.40 (t, 1H, J=2.0 Hz), 4.35 (q, 6H, J=8.0), 3.14 (s, 3H), 1.38 (t, 9H, J=8.0).
Reaction SMILES: [C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][C:7]1([OH:19])[CH:14]2[CH2:15][CH:10]3[CH2:11][C:12]([OH:17])([CH2:16][C:8]1([OH:18])[CH2:9]3)[CH2:13]2.C(N(CC)CC)C.C1COCC1>O>[C:1]([O:19][C:7]1([CH3:6])[CH:14]2[CH2:15][CH:10]3[CH2:11][C:12]([OH:17])([CH2:16][C:8]1([OH:18])[CH2:9]3)[CH2:13]2)(=[O:4])[CH:2]=[CH2:3]
Reactant: C=CC(=O)Cl
Reactant: CC1(O)C2CC3CC(O)(C2)CC1(O)C3
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1CCOC1
Product: C=CC(=O)OC1(C)C2CC3CC(O)(C2)CC1(O)C3
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A total of 6.5 mmole of acrylyl chloride was added dropwise to a mixture of 5 mmole of 2-methyl-1,2,5-adamantanetriol, 7.5 mmole of triethylamine and 50 ml of THF over about 15 minutes. After the completion of addition, the resulting mixture was stirred at room temperature for 1.5 hours. After adding water, the reaction mixture was extracted with ethyl acetate, the organic layer was concentrated, and the concentrate was subjected to column chromatography on a silica gel to thereby yield the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][C:7]1=O)=[O:5])[CH3:2].Cl.[CH:13]1([CH2:17][NH2:18])[CH2:16][CH2:15][CH2:14]1.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[NH:18][CH2:17][CH:13]1[CH2:16][CH2:15][CH2:14]1)=[O:5])[CH3:2]
Reactant: NCC1CCC1
Reactant: CCOC(=O)C1CCCC1=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: O=C([O-])O
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)C1CCCC1NCC1CCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 79.3 %

Procedure:
2-Oxo-cyclopentanecarboxylic acid ethyl ester (0.24 mL, 1.64 mmol) and C-cyclobutyl-methylamine hydrochloride (0.20 g, 1.64 mmol) were dissolved in methanol (8 mL). Sodium acetate (0.27 g, 3.28 mmol) was added followed by 4 Å powdered molecular sieves (0.20 g) and sodium cyanoborohydride (0.21 g, 3.28 mmol). The reaction was stirred at 25° C. for 16 h. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution (20 mL) and ethyl acetate (30 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous sodium bicarbonate solution (10 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, 2-(cyclobutylmethyl-amino)-cyclopentanecarboxylic acid ethyl ester (0.29 g, 1.30 mmol, 79%) as a clear oil. LC-MS (ESI) calcd for C13H23NO2 225.33, found 226.2 [M+H+].
Reaction SMILES: N1C=CC=CC=1.[I:7][C:8]1[CH:16]=[CH:15][C:11]([C:12](Cl)=[O:13])=[CH:10][CH:9]=1.Cl.[CH3:18][NH:19][O:20][CH3:21]>ClCCl>[CH3:18][N:19]([C:12]([C:11]1[CH:15]=[CH:16][C:8]([I:7])=[CH:9][CH:10]=1)=[O:13])[O:20][CH3:21]
Reactant: CNOC
Reactant: O=C(Cl)c1ccc(I)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CON(C)C(=O)c1ccc(I)cc1
Temperature: 25 °C
Yield: 88.1 %

Procedure:
A solution of pyridine (104 g, 1.32 mol) in dichloromethane (150 ml) was added dropwise to an ice-cooled, stirred suspension of 4-iodobenzoyl chloride (251 g, 0.94 mol) and N,O-dimethylhydroxylamine hydrochloride (97 g, 0.94 mol) in dichloromethane (850 ml). The mixture was allowed to warm to room temperature and then stirred for a further 18 hours. The resulting solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (1 l) and this solution then washed sequentially with hydrochloric acid (2M, 3×400 ml) and saturated aqueous sodium bicarbonate solution (300 ml), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by distillation under reduced pressure to give the title compound (241 g) as a yellow oil, b.p. 130° C./13.3 Pa (0.1 mm Hg). δ(CDCl3): 3.32(3H,s), 3.50(3H,s), 7.40(2H,d) 7.72(2H,d).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[O:9])=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18].[CH3:20][CH:21]([NH2:23])[CH3:22]>O>[F:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:23][CH:21]([CH3:22])[CH3:20])=[C:3]([N+:17]([O-:19])=[O:18])[CH:4]=2)=[O:9])=[CH:11][CH:12]=1
Reactant: CC(C)N
Reactant: O=C(c1ccc(F)cc1)c1ccc(Cl)c([N+](=O)[O-])c1
Solvent: O
Product: CC(C)Nc1ccc(C(=O)c2ccc(F)cc2)cc1[N+](=O)[O-]
Yield: 97.2 %

Procedure:
A solution of 14 parts of (4-chloro-3-nitrophenyl)(4-fluorophenyl)methanone in 69 parts of 2-propanamine was stirred overnight at reflux temperature. The reaction mixture was poured into water. The precipitate was filtered off and washed with water, dried, filtered and evaporated, yielding 14.7 parts (97.2%) of (4-fluorophenyl) [4-[(1-methylethyl)amino]-3-nitrophenyl]methanone as a residue (int. 1).