Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[N:31][OH:32])[CH2:29][CH3:30])=[CH:24][CH:23]=1.[C:33]([O:40][CH2:41][CH3:42])(=[O:39])[C:34]([O:36]CC)=O>C1COCC1>[F:21][C:22]1[CH:23]=[CH:24][C:25]([C:28](=[N:31][OH:32])[CH:29]([CH3:30])[C:34](=[O:36])[C:33]([O:40][CH2:41][CH3:42])=[O:39])=[CH:26][CH:27]=1
Reactant: CCC(=NO)c1ccc(F)cc1
Reactant: CCOC(=O)C(=O)OCC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCOC(=O)C(=O)C(C)C(=NO)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 63.1 %

Procedure:
Diisopropylamine (18.2 mL, 129 mmol) was added to 60 mL of THF and cooled with an external ice bath. Butyllithium (50 mL, 126 mmol, 2.5 M in hexanes) was added and the mixture was stirred at 0° C. for 30 min, and brought to room temperature. The resulting LDA solution was added to a mixture of 1-(4-fluorophenyl)propan-1-one oxime (10 g, 59.9 mmol) and THF (50 mL) at 0° C. Following the addition, the reaction mixture was stirred at 0° C. for 1 hour and warmed to room temperature. The mixture was then transferred to a syringe and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (41 mL, 299 mmol) and THF (150 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at room temperature for 18 hours. The mixture was cooled in an ice bath and quenched with 200 mL of 10% hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with EtOAc. The aqueous layer was then neutralized with solid sodium bicarbonate and extracted further with CH2Cl2. The organic layers were combined, dried over MgSO4 and concentrated. The crude oil was purified by chromatography (0-35% EtOAc/hexanes) to give 10.1 g of the title compound. MS: (+) m/z 268.36 (M+1).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[Cl:11][C:12]1[CH:13]=[C:14]([N:18]=[C:19]=[S:20])[CH:15]=[CH:16][CH:17]=1.N1C=CN=C1.[N-]=C=S>C(Cl)(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]([N:6]2[C:5]3[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=3[S:3][CH:2]2[CH3:1])=[S:20])[CH:15]=[CH:16][CH:17]=1
Reactant: S=C=Nc1cccc(Cl)c1
Reactant: Cc1nc2ccccc2s1
Agent: [N-]=C=S
Agent: c1c[nH]cn1
Solvent: ClC(Cl)Cl
Product: CC1Sc2ccccc2N1C(=S)Nc1cccc(Cl)c1

Procedure:
A mixture of 1.5 g. of 2-methylbenzothiazoline, 1.7 g. of 3-chlorophenyl isothiocyanate, about 100 ml. of chloroform, and a catalytic amount of imidazole was heated at reflux for several hours. Since thin layer chromatographic analysis showed that reaction was not complete and that some 3-chlorophenyl isothiocyanate had been lost, an additional 1.2 g. of the isothiocyanate was added to the reaction mixture which then was heated at reflux for about 16 hours. The solvent was distilled under reduced pressure and the residue was recrystallized from ethanol to give N-(3-chlorophenyl)-2-methylbenzothiazoline-3-carbothioamide, m.p. 120°-2°. The following elemental microanalysis was obtained:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH3:36])[C:5]2[N:6]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[N:24]([S:27]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)(=[O:29])=[O:28])[CH:25]=[CH:26][C:19]=34)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.[OH:37][CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(N(CC)CC)C>C(O)CCCC.Cl>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:5]3[C:4]([CH3:36])=[CH:3][C:2]([N:43]4[CH2:44][CH2:45][N:40]([CH2:39][CH2:38][OH:37])[CH2:41][CH2:42]4)=[N:7][N:6]3[C:8]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[N:24]([S:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)(=[O:29])=[O:28])[CH:25]=[CH:26][C:19]=23)=[CH:12][CH:13]=1
Reactant: Cc1cc(Cl)nn2c(-c3ccnc4c3ccn4S(=O)(=O)c3ccccc3)c(-c3ccc(F)cc3)nc12
Reactant: OCCN1CCNCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCCCCO
Product: Cc1cc(N2CCN(CCO)CC2)nn2c(-c3ccnc4c3ccn4S(=O)(=O)c3ccccc3)c(-c3ccc(F)cc3)nc12
Temperature: 150 °C
Reaction time: 48 h
Yield: 35.3 %

Procedure:
A mixture of 0.530 g (1.02 mmol) of 6-chloro-2-(4-fluorophenyl)-8-methyl-3-[1-(phenylsulphonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]imidazo[1,2-b]pyridazine, prepared according to the method described in step 1.4 from Example 1, 0.266 g (2.05 mmol) of 1-(2-hydroxyethyl)piperazine (CAS 103-76-4) and 0.14 ml (1.0 mmol) of triethylamine in 5 ml of pentanol is stirred for 2 days at 150° C. The reaction medium is diluted with 20 ml of an aqueous solution of hydrochloric acid and the solution is washed with ethyl acetate. The aqueous phase is then basified by addition of aqueous ammonia and the product is extracted with dichloromethane. The organic phase is separated, dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The brown oil obtained is then purified by chromatography on a silica gel column (40 g) by eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order to give 0.220 g of 2-{4-[2-(4-fluorophenyl)-8-methyl-3-{1-[phenylsulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazin-6-yl]piperazin-1-yl}ethanol in the form of an amorphous powder which is used in the following step.
Reaction SMILES: [C:1]([CH2:3][NH:4][C:5](=[O:35])[NH:6][C:7]1[CH:8]=[C:9]([C:13]2[C:14]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][N:19](COCC[Si](C)(C)C)[C:15]=3[N:16]=[CH:17][N:18]=2)[CH:10]=[CH:11][CH:12]=1)#[N:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(OCC)(=O)C>[C:1]([CH2:3][NH:4][C:5](=[O:35])[NH:6][C:7]1[CH:8]=[C:9]([C:13]2[C:14]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:10]=[CH:11][CH:12]=1)#[N:2]
Reactant: CCOC(=O)c1cn(COCC[Si](C)(C)C)c2ncnc(-c3cccc(NC(=O)NCC#N)c3)c12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1c[nH]c2ncnc(-c3cccc(NC(=O)NCC#N)c3)c12
Temperature: 45 °C

Procedure:
Ethyl 4-(3-(3-(cyanomethyl)ureido)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (65.4 mg, 0.132 mmol) was mixed with 1 M TBAF in THF (2.64 mL, 2.64 mmol) and heated at 45° C. for 1 hour. The reaction mixture was diluted with ethyl acetate (5 mL) and washed with water (5 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica eluting with 0-20% MeOH/DCM to give ethyl 4-(3-(3-(cyanomethyl)ureido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (EST) calc'd for C18H17N6O3 [M+H]+: 365, found 365. 1H NMR (600 MHz, DMSO-D6) δ 12.96 (bs, 1H), 9.08 (s, 1H), 8.89 (s, 1H), 8.29 (s, 1H), 7.76 (s, 1H), 7.54 (d, J=8.21 Hz, 1H), 7.35 (t, J=7.63 Hz, 1H), 7.20 (d, J=7.63 Hz, 1H), 6.71 (d, J=5.28 Hz, 1H), 4.13 (d, J=5.87 Hz, 2H), 3.86 (q, J=6.8 Hz, 2H), 0.84 (t, J=7.04 Hz, 3H).
Reaction SMILES: [C:1]([C:4]1[S:5]C(Br)=C[CH:8]=1)(=O)[CH3:2].[Br:10][C:11]1[S:15][C:14]([C:16]([CH2:18][C:19]#[N:20])=[O:17])=[CH:13][CH:12]=1.N1CCOCC1.[S]>CC(=O)CC>[NH2:20][C:19]1[S:5][C:4]([CH3:8])=[C:1]([CH3:2])[C:18]=1[C:16]([C:14]1[S:15][C:11]([Br:10])=[CH:12][CH:13]=1)=[O:17]
Reactant: CC(=O)c1ccc(Br)s1
Reactant: N#CCC(=O)c1ccc(Br)s1
Agent: [S]
Solvent: CCC(C)=O
Solvent: C1COCCN1
Product: Cc1sc(N)c(C(=O)c2ccc(Br)s2)c1C
Yield: 51 %

Procedure:
The procedure of Example 1 was followed except that 2-acetyl-5-bromothiophene (Aldrich) was used in place of acetophenone to prepare the corresponding 2-(5-bromothiophene-2-carbonyl)acetonitrile (Steps A and B). 2-Butanone (Aldrich), 2-(5-bromothiophene-2-carbonyl)acetonitrile, morpholine, and sulfur were reacted according to the procedure of Step C, Example 1, to afford the desired compound. Yield: 51%; IR (KBr) cm−1: 3348, 1559, 1448, 1413, 1388, 1318, 1263, 974, 769; 1H NMR (CDCl3):δ 2.16 (s, 6H), 5.90 (bs, 2H), 7.02 (d, J=4 Hz, 1H), 7.11 (d, 1H, J=4 Hz); orange solid, mp: 128–130° C. (petroleum ether).
Reaction SMILES: C1COC2C=CC(NC3C(F)=CN=C(NC4C=CC=C(O)C=4)N=3)=CC=2O1.[NH2:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[C:31]#[N:32].[Cl:36][C:37]1[N:42]=[C:41](Cl)[C:40]([F:44])=[CH:39][N:38]=1>>[Cl:36][C:37]1[N:42]=[C:41]([NH:27][C:28]2[CH:35]=[CH:34][CH:33]=[C:30]([C:31]#[N:32])[CH:29]=2)[C:40]([F:44])=[CH:39][N:38]=1
Reactant: Fc1cnc(Cl)nc1Cl
Reactant: N#Cc1cccc(N)c1
Agent: Oc1cccc(Nc2ncc(F)c(Nc3ccc4c(c3)OCCO4)n2)c1
Product: N#Cc1cccc(Nc2nc(Cl)ncc2F)c1

Procedure:
In a manner analogous to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, 3-aminobenzonitrile (142 mg, 1.2 mmol) and 2,4-dichloro-5-fluoropyrimidine (100 mg, 0.6 mmol) gave 2-chloro-N4-(3-cyanophenyl)-5-fluoro-4-pyrimidineamine (128, mg, 86%) as a white solid. The reaction of 2-chloro-N4-(3-cyanophenyl)-5-fluoro-4-pyrimidineamine (50 mg, 0.2 mmol) and 3-aminophenol (66 mg, 0.6 mmol) gave N4-(3-cyanophenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine (40 mg, 62%). 1H NMR (acetone-d6): δ 6.48 (ddd, J=0.9, 2.4 and 7.8 Hz, 1H), 7.10 (t, J=8.1 Hz, 1H), 7.18 (ddd, J=1.2, 2.1 and 8.1 Hz, 1H), 7.33 (t, J=2.1 Hz, 1H), 7.45 (dt, J=1.2 and 7.8 Hz, 1H), 7.54 (t, J=8.1 Hz, 1H), 8.08 (d, J=3.3 Hz, 1H), 8.14 (ddd, J=1.5, 2.7 and 8.4 Hz, 1H), 8.39 (t, J=2.1 Hz, 1H), 8.58 (s, 1H, NH), 8.84 (s, 1H, NH); 19F NMR (282 MHz, acetone-d6): δ −167.41; LCMS: ret. time: 17.75 min.; purity: 92.39%; MS (m/e): 322.59 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20]O)[C:6]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:8][C:7]=2[CH:19]=1.B(Br)(Br)[Br:23]>ClCCl>[Br:23][CH2:20][C:5]1[C:6]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:8][C:7]=2[CH:19]=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: BrB(Br)Br
Reactant: COc1ccc(-c2cc3cc(OC)cc(CO)c3o2)cc1
Solvent: ClCCl
Product: COc1ccc(-c2cc3cc(OC)cc(CBr)c3o2)cc1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Benzyl Alcohol 3 (1.02 g, 3.59 mmole) was dissolved in dichloromethane (70 mL) and cooled to −78° C. in an dry ice/acetone bath. Boron tribromide (1.0 M in dichloromethane), (3.95 mL, 3.95 mmole) was added drop wise over 15 minutes. After 30 minutes, the light orange solution was allowed to come to room temperature and reacted for an additional four hours. The solution was concentrated and added to saturated sodium bicarbonate, and extracted with ethyl acetate. Organic layers were combined and washed with water and brine, dried over magnesium sulfate. The organic phases were concentrated and the residue was loaded on to silica gel and chromatographed with silica gel (hexanes:ethyl acetate, 9:1) to afford 2.91 g (81%) of benzyl bromide17 as a white solid: Mp=158–160° C.; 1H NMR (DMSO-6) δ 7.88(d, 2 H, J=8.8 Hz), 7.23 (s, 1 H), 7.11 (d, 2 H, J=2.5 Hz), 7.09 (d, 2 H, J=8.9 Hz), 6.99 (d, 1 H, J=2.5 Hz), 4.96 (s, 2 H), 3.82 (s, 3 H), 3.80 (s, 3 H).
Reaction SMILES: O[C:2]1[C:3](=[O:12])[O:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C1C[O:16]CC1>[OH-].[Pd+2].[OH-]>[OH:16][C:7]1[CH:6]=[C:5]2[C:10]([CH2:11][CH2:2][C:3](=[O:12])[O:4]2)=[CH:9][CH:8]=1
Reactant: O=c1oc2ccccc2cc1O
Reactant: C1CCOC1
Agent: [Pd+2]
Agent: [OH-]
Product: O=C1CCc2ccc(O)cc2O1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of hydroxycoumarin (2.0 g, TCI) in anhydrous THF (50 ml) was added with 10% palladium hydroxide/activated carbon (1.0 g, WAKO), and stirred at room temperature for 2 hours under hydrogen atmosphere. The atmosphere was replaced with nitrogen gas, and then the insoluble matters were removed by filtration through Celite. The solvent was evaporated under reduced pressure to obtain the title compound (2.0 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH:63]([N:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)=[O:64]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:68]1[CH2:69][CH2:70][N:65]([CH:63]=[O:64])[CH2:66][CH2:67]1)=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: O=CN1CCNCC1
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2cc(C(=O)N3CCN(C=O)CC3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 4-formyl-piperazine in DMSO at ambient temperature.
Reaction SMILES: [NH2:1]OS(O)(=O)=O.[OH:7][CH:8]([CH2:16][O: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][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[OH-].[Na+]>O1CCCC1.O>[NH2:1][N:13]1[CH2:14][CH2:15][N:10]([CH2:9][CH:8]([OH:7])[CH2:16][O: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][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:11][CH2:12]1
Reactant: CCCCCCCCCCCCCCCCCCOCC(O)CN1CCNCC1
Reactant: NOS(=O)(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCCCCCCCCCCCCOCC(O)CN1CCN(N)CC1

Procedure:
A solution of hydroxylamine-O-sulfonic acid (0.17 g, 1.5 mmol) in 1:1 tetrahydrofuran-water (10 mL) is added dropwise to a mixture of 1-[2'-hydroxy-3'-octadecyloxypropyl]-piperazine (3.0 g, 7.3 mmol) and sodium hydroxide (0.29 g) in 1:1 tetrahydrofuran-water (30 mL) at 15° C. over a 30 minute period under a nitrogen atmosphere. The resultant mixture is stirred at 15° C. for 2 hours. Three additional portions of NaOH (0.29 g each) are then added to the mixture. The reaction mixture is extracted with dichloromethane, dried over NaOH, concentrated and chromatographed to afford 1-N-Amino-4-N-[2'-hydroxy-3'-octadecyloxypropyl]-piperazine.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:13])=[C:7]2[C:12]=1[CH2:11][NH:10][CH2:9][CH2:8]2.[C:14]1([C@@H:20]2[CH2:22][C@H:21]2[C:23](O)=[O:24])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CN(C)C1C=CN=CC=1.CCOC(C)=O>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:13])=[C:7]2[C:12]=1[CH2:11][N:10]([C:23]([C@@H:21]1[CH2:22][C@H:20]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:24])[CH2:9][CH2:8]2
Reactant: O=C(O)[C@@H]1C[C@H]1c1ccccc1
Reactant: Fc1ccc(Br)c2c1CCNC2
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C([C@@H]1C[C@H]1c1ccccc1)N1CCc2c(F)ccc(Br)c2C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 8-bromo-5-fluoro-1,2,3,4-tetrahydro-isoquinoline hydrochloride (200 mg, 0.75 mmol, 1.0 eq.) and the acid (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (122 mg, 0.75 mmol, 1.0 eq.) in DMF (9 mL) was treated with 4-(dimethylamino)pyridine (367 mg, 3.00 mmol, 4.0 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (216 mg, 1.13 mmol, 1.5 eq.) and the resulting solution was stirred at r.t. for 18 hours. The reaction mixture was diluted with AcOEt (70 mL). The diluted solution was washed with 1N aq. HCl (3×30 mL), sat. aq. NaCl soln. (1×30 mL), dried over MgSO4, filtered, and concentrated in vacuo to give the desired compound as a pale yellow oil. The product was used without further purification.
Reaction SMILES: [CH2:1]([Sn:5]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:16][CH2:17][CH2:18][CH3:19])/[CH:6]=[CH:7]/[C:8]([CH3:15])([OH:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:2][CH2:3][CH3:4].N1C=CN=C1.Cl[Si:30]([CH3:33])([CH3:32])[CH3:31]>CN(C)C=O>[CH2:20]([Sn:5]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:1][CH2:2][CH2:3][CH3:4])/[CH:6]=[CH:7]/[C:8]([CH3:15])([O:14][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:21][CH2:22][CH3:23]
Reactant: C[Si](C)(C)Cl
Reactant: CCCCCC(C)(O)/C=C/[Sn](CCCC)(CCCC)CCCC
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CCCCCC(C)(/C=C/[Sn](CCCC)(CCCC)CCCC)O[Si](C)(C)C

Procedure:
The vinylstannane is treated with imidazole, and chlorotrimethylsilane in dimethylformamide by the procedure of Example 1 to provide (E)-1-tri-n-butylstannyl-3-methyl-3-trimethylsilyloxy-1-octene as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([N:8]([CH2:17][CH2:18][CH2:19][CH3:20])[CH:9]2[CH2:13][N:12]([CH2:14][CH3:15])[CH2:11][CH:10]2[OH:16])=[O:7])=[CH:4][CH:3]=1.[OH-].[K+].O>CO>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([N:8]([CH2:17][CH2:18][CH2:19][CH3:20])[C@@H:9]2[CH2:13][N:12]([CH2:14][CH3:15])[CH2:11][C@H:10]2[OH:16])=[O:7])=[CH:4][CH:3]=1
Reactant: CCCCN(C(=O)c1ccc(Cl)cc1)C1CN(CC)CC1O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCCCN(C(=O)c1ccc(Cl)cc1)[C@@H]1CN(CC)C[C@H]1O
Yield: 89 %

Procedure:
A mixture of 7.0 g (0.015 mole) of trans-4-chlorobenzoic acid ester with 4-[(4-chlorobenzoyl)(n-butyl)amino]1-ethyl-3-pyrrolidinol, 0.9 g (0.016 mole) of potassium hydroxide, 15 ml of water and 60 ml of methanol was heated on a steam bath for 1 hr, then concentrated to approximately 10 ml volume under reduced pressure. The residue was partitioned between water and methylene chloride. The organic layer was separated, dried and concentrated under reduced pressure. The crystalline residue was recrystallized from isopropyl ether to give 4.3 g (89%) of white powder; m.p. 96.5°-98.0° C.
Reaction SMILES: CCN(CC)CC.Cl.[S:9]1[C:13]([NH2:14])=[CH:12][N:11]=[CH:10]1.[CH3:15][C:16](OC(C)=O)=[O:17]>C(Cl)Cl>[S:9]1[C:13]([NH:14][C:16](=[O:17])[CH3:15])=[CH:12][N:11]=[CH:10]1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cncs1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1cncs1
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.1 %

Procedure:
To a solution of Et3N (0.31 mL, 2.20 mmol) and thiazol-5-amine hydrochloride (0.2 g, 1.46 mmol) from example 1.2 in DCM (10 mL) was added Ac2O (0.21 mL, 2.20 mmol). The mixture was stirred at room temperature for 3 h and then concentrated. The resulting mixture was deposited onto silica gel and loaded onto a silica gel column and eluted with EA to give the title compound (0.14 g, 0.98 mmol, 70%).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:15]([O:17][CH3:18])=[O:16].C(O)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].CO>C(O)(C)C>[CH:6]1[C:5]2[C:10](=[CH:1][C:2]([C:15]([O:17][CH2:18][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])=[O:16])=[CH:3][CH:4]=2)[CH:9]=[CH:8][C:7]=1[C:11]([O:13][CH2:14][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])=[O:12]
Reactant: CCCCCCCCCCCCCCCCCCO
Reactant: COC(=O)c1ccc2cc(C(=O)OC)ccc2c1
Solvent: CC(C)O
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCOC(=O)c1ccc2cc(C(=O)OCCCCCCCCCCCCCCCCCC)ccc2c1
Temperature: 160 °C
Yield: 85.8 %

Procedure:
To a 3 neck 100 mL round bottomed flask equipped with a Dean Stark trap and condenser, thermocouple and argon inlet was added dimethyl naphthalene-2,6-dicarboxylate (10 grams, 40.94 mmoles, available from Sigma Aldrich), stearyl alcohol (22.15 grams, 81.89 mmoles, available from Spectrum Chemical), Fascat 4100 (0.03 grams, 0.1 wt %, available from Arkema Inc) and Xylenes (50 ml, available from Sigma Aldrich). The mixture was slowly heated under argon to 160° C. during which reagents melted/dissolved. The temperature was raised to 180° C. The reaction mixture was stirred at 180° C. overnight (˜20 hours) during which 46 mL of a mixture of xylenes and methanol was collected. Vacuum was applied (1-2 mm-Hg) for about 10 minutes during which an additional 5 mL of a mixture of Xylenes and methanol was collected. The solution was cooled under argon to about 140° C. and discharged in an aluminum tray where it was allowed to cool to room temperature to give product as an off-white solid. The product was transferred to a 1 L Erlenmeyer flask, about 100 mL of isopropyl alcohol was added, heated to about 100° C. during which product dissolved. The solution was cooled to room temperature during which product crystallized out, filtered and dried on a vacuum pump overnight to give 25.33 grams product as an off-white solid (86% yield). The product was shown to be pure by 1H NMR with trace amounts of the mono-ester. Physical properties of this compound are shown in Table 2 above. The FIGURE shows the rheological profile.
Reaction SMILES: C1(C(C(C2C=CC=CC=2)=O)=O)C=CC=CC=1.[CH3:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([CH:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[OH:27])=[O:25])=[CH:20][CH:19]=1>O.N1C=CC=CC=1>[CH3:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([C:26]([C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)=[O:27])=[O:25])=[CH:22][CH:23]=1
Reactant: Cc1ccc(C(=O)C(O)c2ccc(C)cc2)cc1
Agent: O=C(C(=O)c1ccccc1)c1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: Cc1ccc(C(=O)C(=O)c2ccc(C)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
4,4′-Dimethylbenzil was prepared on the basis of a known method for benzil (L. F. Tietze, Th. Eicher, Reaktionen und Synthesen[Reactions and Syntheses], R. Stierlein, Chem. Ber. 22/1 (1889) 37). 420 g of CuSO4·5H2O (1.68 mol) were dissolved in a mixture of 350 ml of water and 400 ml of pyridine bases while heating. 190 g (0.79 mol) of crude 4,4′-dimethylbenzoin were added to the still warm solution, and refluxing was effected for 4 hours. After cooling to room temperature, the crude product was filtered off and washed with water. The filter residue was taken up in ether, filtered and dried with Na2SO4. After the solution had been evaporated down to about 500 ml, 4,4′-dimethylbenzil crystallized out in the form of pale yellow crystals. Depending on their use, they were recrystallized from ethanol (yield 119.9 g (64%, based on crude 4,4′-dimethylbenzoin used); m.p.: 104° C., literature: 104-105° C. The IR spectrum of 4,4′-dimethylbenzil is shown in FIG. 9.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].[C:10]([CH2:12][C:13](OCC)=[O:14])#[N:11]>C(OCC)(=O)C.O1CCCC1>[C:10]([CH2:12][C:13]([NH:5][C:4]1[CH:6]=[CH:7][C:8]([F:9])=[C:2]([F:1])[CH:3]=1)=[O:14])#[N:11]
Reactant: CCOC(=O)CC#N
Reactant: Nc1ccc(F)c(F)c1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: N#CCC(=O)Nc1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
A mixed solution of 3,4-difluoroaniline (10 g, 77.5 mmol) and ethyl cyanoacetate (10.5 g, 92.9 mmol) was heated to 180° C. and stirred for 8 hr. After cooling to room temperature, the mixture was dissolved in ethyl acetate/tetrahydrofuran and washed with water and saturated brine in this order. The mixture was dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the obtained residue was washed with ethyl acetate and collected by filtration to give the title compound (7.6 g, 56%) as a yellow solid.
Reaction SMILES: C(N(CC)CC)C.[CH2:8]([N:15]1[C:23]([OH:24])=[N:22][C:21]2[C:16]1=[N:17][CH:18]=[N:19][C:20]=2[NH2:25])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl[C:27]([O:29][CH3:30])=[O:28]>C1COCC1>[CH2:8]([N:15]1[C:23]([O:24][C:27]([O:29][CH3:30])=[O:28])=[N:22][C:21]2[C:16]1=[N:17][CH:18]=[N:19][C:20]=2[NH2:25])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COC(=O)Cl
Reactant: Nc1ncnc2c1nc(O)n2Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)Oc1nc2c(N)ncnc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.2 %

Procedure:
Triethylamine (202 mg, 2 mmol) and N,N-dimethylaminopyridine (111 mg 0.5 mmol) were added to 9-benzyl-8-hydroxyadenine (241 mg, 1 mmol) dissolved in anhydrous THF (20 ml). After stirring at room temperature for 1 h, methyl chloroformate (113 mg, 1.2 mmol) was added thereto, and the mixture was stirred overnight at room temperature. The resulting reaction mixture was extracted by ethyl acetate (50 ml) and water (50 ml), and the resulting organic layer was concentrated under vacuum followed by addition of ether (20 ml) to obtain the desired compound as crystals (300 mg, Yield: 100%).