Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].C(CC(=O)C(C)(C)C)(=O)C(C)(C)C.Br[C:32]1[CH:33]=[N:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[CH:37][CH:36]=2>CN1CCCC1=O.[Cu]Cl>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[O:11][C:32]1[CH:33]=[N:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[CH:37][CH:36]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccccc1O
Reactant: Brc1cnc2ccccc2c1
Agent: Cl[Cu]
Agent: CC(C)(C)C(=O)CC(=O)C(C)(C)C
Agent: O=C([O-])[O-]
Solvent: CN1CCCC1=O
Product: CC(C)(C)c1ccccc1Oc1cnc2ccccc2c1
Temperature: 130 °C
Reaction time: 24 h
Yield: 7.1 %

Procedure:
0.60 g of 2-t-butylphenol, 1.3 g of cesium carbonate, 0.07 g of dipivaloylmethane, 0.42 g of 3-bromoquinoline, and 0.20 g of copper (I) chloride were dissolved in 4 ml of N-methylpyrrolidone, and the mixture was stirred for one day at 130° C. The resultant was purified by silica gel column chromatography, and 0.04 g of 3-(2-t-butyl-phenoxy)-quinoline (Compound Number 14) was obtained.
Reaction SMILES: COC[O:4][C:5]1[C:6]([CH3:14])=[C:7](B(O)O)[CH:8]=[CH:9][CH:10]=1.[CH3:15][C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([CH3:34])[C:25]=1OS(C(F)(F)F)(=O)=O)[C:19]([O:21][CH3:22])=[O:20].C(=O)([O-])[O-].[K+].[K+]>CO.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>[OH:4][C:5]1[C:6]([CH3:14])=[C:7]([C:25]2[C:24]([CH3:34])=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=2[CH3:15])[CH:8]=[CH:9][CH:10]=1
Reactant: COCOc1cccc(B(O)O)c1C
Reactant: COC(=O)c1cc(C)c(OS(=O)(=O)C(F)(F)F)c(C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)c1cc(C)c(-c2cccc(O)c2C)c(C)c1

Procedure:
In a manner similar to that of Example 11(d), by reaction of 1.5 g (7.6 mmol) of 3-methoxymethoxy-2-methylbenzene-1-boronic acid (described in Example 11(c)) with 2 g (6.4 mmol) of methyl 3,5-dimethyl-4-trifluoromethanesulphonyloxybenzoate, 7.7 mL of 2.0M potassium carbonate solution and 370 mg (0.32 mmol) of tetrakis(triphenylphosphine)palladium, followed by deprotection in methanol, the desired product is obtained in the form of a white solid (m.p.=149° C.; m=1.34 g; Y=67%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl-].[Al+3].[Cl-].[Cl-].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][CH3:26].Cl>S(Cl)(Cl)=O.ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([C:22]2[CH:23]=[CH:24][C:19]([O:18][CH3:17])=[C:20]([O:25][CH3:26])[CH:21]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COc1ccccc1OC
Reactant: O=C(O)Cc1ccc(Cl)c(Cl)c1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(C(=O)Cc2ccc(Cl)c(Cl)c2)cc1OC
Temperature: 25 °C
Reaction time: 17 h

Procedure:
A mixture of (3,4-dichloro-phenyl)-acetic acid (11.14 g, 54.33 mmol) and anhydrous DMF (1.45 ml) in thionyl chloride (137 ml) was stirred at RT, under nitrogen, for 17 h. The excess of thionyl chloride was removed under vacuum. Anhydrous toluene was added to the residue, which was again concentrated in vacuum (repeated two more times). Powdered anhydrous aluminium chloride (11.57 g, 86.72 mmol) was added portionwise (exothermic reaction) to a stirred mixture of 1,2-dimethoxy-benzene (6.92 ml, 54.34 mmol) and the previous acyl chloride in anhydrous dichloromethane (120 ml). An exothermic reaction occurred and the reaction mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool to RT and was then poured into a mixture of ice (67 g) and aqueous 7.5N HCl (64 ml). The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated to dryness to give a brown residue (oil and solid). After a further drying (HV), anhydrous diethylether was added and a beige solid precipitated. The beige solid was filtered and further dried (8.33 g, 47%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][C:6]([S:12]([NH2:15])(=[O:14])=[O:13])=[CH:5][CH:4]=1>[Ni]>[NH2:9][C:8]1[CH:7]=[C:6]([S:12]([NH2:15])(=[O:13])=[O:14])[CH:5]=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: COc1ccc(S(N)(=O)=O)cc1[N+](=O)[O-]
Agent: [Ni]
Product: COc1ccc(S(N)(=O)=O)cc1N

Procedure:
0.1 mol (23.2 g) of 4-methoxy-5-nitrobenzenesulphonamide is dissolved in 300 ml of absolute alcohol and 10 g of nickel prepared by the RANEY process are added. The solution is hydrogenated at atmospheric pressure and at room temperature while stirring. The catalyst is separated and then washed with two portions of 50 ml of alcohol; the solution is concentrated under reduced pressure; the 3-amino-4-methoxybenzenesulphonamide crystallizes.
Reaction SMILES: NC1C(NCCSCC2C=C(CN(C)C)SC=2)=NS(=O)N=1.[NH2:22][C:23]1[C:27]([NH:28][CH2:29][CH2:30][S:31][CH2:32][C:33]2[S:34][C:35]([CH2:39][N:40]([CH3:42])[CH3:41])=[C:36]([CH3:38])[CH:37]=2)=[N:26][S:25](=O)[N:24]=1>>[NH2:22][C:23]1[C:27]([NH:28][CH2:29][CH2:30][S:31][CH2:32][C:33]2[S:34][C:35]([CH2:39][N:40]([CH3:41])[CH3:42])=[C:36]([CH3:38])[CH:37]=2)=[N:26][S:25][N:24]=1
Reactant: Cc1cc(CSCCNC2=NS(=O)N=C2N)sc1CN(C)C
Agent: CN(C)Cc1cc(CSCCNC2=NS(=O)N=C2N)cs1
Product: Cc1cc(CSCCNc2nsnc2N)sc1CN(C)C

Procedure:
The general procedure of Example 5 is repeated except that the 3-amino-4-{2-[(5-dimethylaminomethyl-3-thienyl)methylthio]ethylamino}-1,2,5-thiadiazole 1-oxide utilized therein is replaced by an equimolar amount of 3-amino-4-{2-[(5-dimethylaminomethyl-4-methyl-2-thienyl)methylthio]ethylamino}-1,2,5-thiadiazole 1-oxide [prepared according to the general procedure described in U.S. Pat. No. 4,374,248], and the title compound is thereby produced.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:21]([CH2:22][C:23]([OH:25])=[O:24])[N:20]=[C:19]([C:26]([F:29])([F:28])[F:27])[CH:18]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[CH3:30][N:31]([CH3:35])[CH2:32][CH2:33]O.C(N(CC)CC)C>CS(C)=O.O>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:21]([CH2:22][C:23]([O:25][CH2:33][CH2:32][N:31]([CH3:35])[CH3:30])=[O:24])[N:20]=[C:19]([C:26]([F:29])([F:27])[F:28])[CH:18]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])=[O:4]
Reactant: CN(C)CCO
Reactant: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(F)(F)F)nn3CC(=O)O)cc2)c1
Solvent: O
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CN(C)CCOC(=O)Cn1nc(C(F)(F)F)cc1-c1ccc(-c2cccc(S(C)(=O)=O)c2)cc1
Reaction time: 8 h
Yield: 6.4 %

Procedure:
To a stirred solution of compound 38 (0.2 g, 0.471 mmol), 2-(dimethylamino)ethanol (0.14 mL, 1.41 mmol) and triethylamine (0.126 mL, 0.942 mmol) in DMSO (5 mL) at RT was added Pybop (0.360 g, 0.706 mmol) and the reaction mixture stirred overnight. The reaction was then diluted with water (30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layer was washed with saturated brine, dried over sodium sulphate and concentrated. The crude reaction mixture was purified by column chromatography using 3% methanol in dichloromethane to afford 39 (15 mg, 6%). LCMS: 496.25 (M+1)+; 1H NMR (CD3OD, 400 MHz) δ 8.23 (s, 1H), 8.05 (d, 1H, J=8 Hz), 8.01 (d, 1H, J=7.6 Hz), 7.88 (d, 1H, J=8.4 Hz), 7.78 (t, 3H, J=8 Hz), 7.64 (d, 2H, J=8 Hz), 6.84 (s, 1H), 5.2 (s, 2H), 4.5 (t, 2H, J=4.8 Hz), 3.49 (d, 2H, J=4.8 Hz), 3.20 (s, 3H), 2.9 (s, 6H).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.C[O:12][C:13]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[CH:23]=2)[CH:18]=[CH:17][CH:16]=1)=O>C(Cl)Cl>[Cl:25][C:22]1[CH:23]=[C:24]2[C:19]([CH:18]=[CH:17][CH:16]=[C:15]2[CH2:13][OH:12])=[CH:20][CH:21]=1
Reactant: COC(=O)c1cccc2ccc(Cl)cc12
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: ClCCl
Product: OCc1cccc2ccc(Cl)cc12
Reaction time: 1 h

Procedure:
A 0.7M diisobutylaluminium hydride solution in CH2Cl2 is added dropwise at −78° to 22 g of 7-chloro-naphthalene-1-carboxylic acid methyl ester in CH2Cl2. After stirring at −78° for 1 hour, the mixture obtained is warmed up to 0°, quenched with aq. 10% sodium tartrate solution and stirred for further few minutes. The organic phase obtained is separated, washed with brine, dried and solvent is evaporated. The residue obtained is purified by flash chromatography on silica gel (eluent: cyclohexane/EtOAc 8/1 to 4/1) and the title compound is obtained.
Reaction SMILES: CS[C:3]1[S:4]/[C:5](=[CH:9]\[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)/[C:6](=[O:8])[N:7]=1.[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH:25]([NH2:27])[CH3:26].CCN(C(C)C)C(C)C>>[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH:25]([NH:27][C:3]1[S:4]/[C:5](=[CH:9]\[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)/[C:6](=[O:8])[N:7]=1)[CH3:26]
Reactant: CC(N)c1cccs1
Reactant: CSC1=NC(=O)/C(=C/c2ccc3ncccc3c2)S1
Solvent: CCN(C(C)C)C(C)C
Product: CC(NC1=NC(=O)/C(=C/c2ccc3ncccc3c2)S1)c1cccs1

Procedure:
Similar procedure as described in example 1b was used, starting from 2-methylsulfanyl-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one, 1-thiophen-2-yl-ethylamine and DIEA to give 2-(1-thiophen-2-yl-ethylamino)-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one. LC-MS m/e 366 (MH+).
Reaction SMILES: [S:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]([NH2:38])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:8][CH:7]=2)=[CH:4][N:3]=[CH:2]1.CN1CCOCC1.[CH3:46][O:47][C:48]([NH:50][C@H:51]([C:55](O)=[O:56])[CH:52]([CH3:54])[CH3:53])=[O:49].[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C>CN(C=O)C>[S:1]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]([CH2:12][N:13]([NH:38][C:55](=[O:56])[C@H:51]([CH:52]([CH3:53])[CH3:54])[NH:50][C:48]([O:47][CH3:46])=[O:49])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C:32]([CH3:34])([CH3:35])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:10][CH:11]=2)=[CH:4][N:3]=[CH:2]1
Reactant: COC(=O)N[C@H](C(=O)O)C(C)C
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(N)Cc1ccc(-c2cncs2)cc1)C(C)(C)C
Agent: CN(C)C(On1ccccc1=O)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: COC(=O)N[C@H](C(=O)NN(Cc1ccc(-c2cncs2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Under an argon atmosphere, 344 mg of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane and 191 μl (1.74 mmol) of NMM in 5.6 ml of DMF are added to 122 mg (0.696 mmol) of N-methoxycarbonyl-(L)-valine and 173 mg (0.58 mmol) of TPTU in 2.9 ml of DMF and the mixture is stirred at room temperature for 16 hours. The reaction mixture is poured into ice-water, stirred for 30 min and filtered. Column chromatography of the residue (SiO2 ; methylene chloride/THF 4:1) and stirring in ether yield the title compound: m.p: 134°-135° C.; HPLC20-100 : tRet =14.0; FAB MS (M+H)+ =697.
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([CH:7]=[C:8]([C:18]#[N:19])[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:3][CH:2]=1.[CH:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O)C>CN(C)C=O>[C:1]1([CH:20]=[CH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:2]=[CH:3][C:4]([CH:7]=[C:8]([C:18]#[N:19])[S:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[CH:5][CH:6]=1
Reactant: O=Cc1ccccc1
Reactant: Cc1ccc(C=C(C#N)S(=O)(=O)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCO
Product: N#CC(=Cc1ccc(C=Cc2ccccc2)cc1)S(=O)(=O)c1ccccc1
Yield: 63 %

Procedure:
12.48 g (20 mmole) of the triphenylphosphonium bromide of Example 1 c) were dissolved in 200 ml of absolute dimethylformamide at 70° C, by stirring and under an atmosphere of nitrogen. After the mixture had cooled to 30° to 35° C, 2.24 g (20 mmole) of potassium-tert. butylate were introduced and the whole was stirred again for 5 minutes. The solution of 2.12 g (20 mmole) of benzaldehyde in 20 ml of absolute dimethylformamide was added dropwise within 10 minutes to the violet solution and the whole was further heated for 4 hours to 100° C under an atmosphere of nitrogen. After cooling, the potassium bromide separated was filtered off with suction and the dimethylformamide was eliminated by destillation on a rotary vaporator and under a vacuum produced by a water jet. The residue was combined with 200 ml of hot ethanol. After cooling, 4.65 g of weakly yellow crystals of 1-(stilbene-4-yl)-2-cyano-2-phenylsulfonylethylene having a melting point of 179° to 183° C (corresponding to a yield of 63% of the theory), were obtained. ##STR17##
Reaction SMILES: BrC1C=CC(C2(C3C=CC(O)=CC=3)CC2)=CC=1.BrC/C=C/CBr.Br[CH2:25]/[CH:26]=[CH:27]/[CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2([C:39]3[CH:44]=[CH:43][C:42]([Br:45])=[CH:41][CH:40]=3)[CH2:38][CH2:37]2)=[CH:32][CH:31]=1.[CH2:46]([NH:49][CH3:50])[CH:47]=[CH2:48]>>[CH2:46]([N:49]([CH2:25]/[CH:26]=[CH:27]/[CH2:28][O:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]2([C:39]3[CH:40]=[CH:41][C:42]([Br:45])=[CH:43][CH:44]=3)[CH2:38][CH2:37]2)=[CH:34][CH:35]=1)[CH3:50])[CH:47]=[CH2:48]
Reactant: C=CCNC
Reactant: BrC/C=C/COc1ccc(C2(c3ccc(Br)cc3)CC2)cc1
Agent: BrC/C=C/CBr
Agent: Oc1ccc(C2(c3ccc(Br)cc3)CC2)cc1
Product: C=CCN(C)C/C=C/COc1ccc(C2(c3ccc(Br)cc3)CC2)cc1

Procedure:
from 4-(1-(4-bromo-phenyl)-cyclopropyl)-phenol (Ex. Eg) and (E)-1,4-dibromo-2-butene via (E)-1-[4-(4-bromo-but-2-enyloxy)-phenyl]-1-(4-bromo-phenyl)-cyclopropane and reaction with N-allyl-methyl-amine there is obtained (E)-allyl-[4-[4-[1-(4-bromo-phenyl)-cyclopropyl]-phenoxy]-but-2-enyl]-methyl-amine which is converted into the fumarate, MS: m/e 412 (M+H+, 1Br).
Reaction SMILES: O1CCOCC1.[F:7][C:8]([F:12])([F:11])[CH2:9][NH2:10].CCN(C(C)C)C(C)C.Cl[S:23]([CH2:26][CH2:27][NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)(=[O:25])=[O:24]>C(#N)C>[F:7][C:8]([F:12])([F:11])[CH2:9][NH:10][S:23]([CH2:26][CH2:27][NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)(=[O:25])=[O:24]
Reactant: O=C(NCCS(=O)(=O)Cl)OCc1ccccc1
Reactant: NCC(F)(F)F
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C(NCCS(=O)(=O)NCC(F)(F)F)OCc1ccccc1
Reaction time: 0.33 h
Yield: 39 %

Procedure:
To a dioxane (1 mL) solution of 2,2,2-trifluoroethanamine (80 mg, 0.81 mmol) and DIEA (0.28 mL, 1.6 mmol) at 0° C. was added benzyl (2-(chlorosulfonyl)ethyl)carbamate (150 mg, 0.54 mmol) in acetonitrile (1 mL). The reaction was allowed to reach room temperature over a period of 20 minutes. The reaction mixture was concentrated under reduced pressure, and the residue purified using reverse phase HPLC (YMC Sunfire 5u (C18) 30×100 mm, 0-100% ACN (90% in H2O, 0.1% TFA) using gradient over 16 min with flow rate 40 mL/min and UV detection at 220 nm) to give Compound B30a (95 mg, 39% yield). HPLC: RT=3.84 (LCMS Method M). MS (ES): m/z=340.9 [M+H]+. 1H NMR (500 MHz, CHLOROFORM-d) d 7.43-7.34 (m, 5H), 5.28 (br. s., 2H), 5.15 (s, 2H), 3.86-3.68 (m, 4H), 3.35-3.24 (m, 2H).
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:18][C@H:17]([OH:19])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:37])[C@@H:15]2[CH2:20][CH2:21][C@H:22]2[O:27][C:26](=[O:28])[CH2:25][C@H:24]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:23]2)=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:38]([C:40]([CH2:47][CH3:48])([CH2:44][CH:45]=[CH2:46])[C:41](Cl)=[O:42])[CH3:39]>>[Si:1]([O:8][C@H:9]1[CH2:18][C@H:17]([O:19][C:41](=[O:42])[C:40]([CH2:47][CH3:48])([CH2:38][CH3:39])[CH2:44][CH:45]=[CH2:46])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:37])[C@@H:15]2[CH2:20][CH2:21][C@H:22]2[O:27][C:26](=[O:28])[CH2:25][C@H:24]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:31])[CH3:32])[CH2:23]2)=[CH:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Reactant: C=CCC(CC)(CC)C(=O)Cl
Product: C=CCC(CC)(CC)C(=O)O[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O3)[C@H]21
Yield: 78.6 %

Procedure:
A procedure similar to that described in Example 6, above, was followed, but using 2.0 g (3.6 mmol) of (4R,6R)-6-{2-[(1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-hydroxy-2-methyl-1-naphthyl]-ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above] and 3.17 g (18.1 mmol) of 2,2-diethyl-4-pentenoyl chloride, to provide 1.95 g of the title compound.
Reaction SMILES: Cl.[CH3:2][NH:3][CH3:4].[OH-].[Na+].[CH2:7]([C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1)[CH3:8]>O>[CH3:2][N:3]([CH3:4])[C:13](=[O:14])[C:12]1[CH:16]=[CH:17][C:9]([CH2:7][CH3:8])=[CH:10][CH:11]=1
Reactant: CNC
Reactant: CCc1ccc(C(=O)Cl)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCc1ccc(C(=O)N(C)C)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 98.2 %

Procedure:
In 50 g of water is dissolved 36.0 g (442 mmole) of dimethylamine hydrochloride. 50 g of ice and 36 g (450 mmole) of 50% sodium hydroxide solution are added. While maintaining the internal temperature below 10° C, 35 g (208 mmole) of 4-ethylbenzoyl chloride is added. The mixture is stirred 20 minutes, extracted with ethyl ether, dried over anhydrous magnesium sulfate and concentrated in vacuo to yield 36.2 g of N,N-dimethyl-4-ethylbenzamide.
Reaction SMILES: Br.[C:2]([O:5][C@H:6]1[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1[O:8][C:9](=[O:11])[CH3:10])(=[O:4])[CH3:3]>C(O)(=O)C>[C:2]([O:5][C@@H:6]1[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1[O:8][C:9](=[O:11])[CH3:10])(=[O:4])[CH3:3]
Reactant: CC(=O)OC[C@H]1O[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OCc2ccccc2)[C@@H]1OC(C)=O
Agent: Br
Solvent: CC(=O)O
Product: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OCc2ccccc2)[C@@H]1OC(C)=O
Temperature: 0 °C
Yield: 101.4 %

Procedure:
Hydrogen bromide (33% solution in acetic acid) (100 mL) was slowly added to the 69 g of 1,2,4,6-tetra-O-acetyl-3-O-benzyl-α-D-glucopyranose from Step 4 and cooled to 0° C. to produce a solution of 1,2,4,6-tetra-O-acetyl-3-O-benzyl-β-D-glucopyranose (70 g) in acetic acid (140 mL). The mixture was stirred at 0° C. for 1 hour and then diluted with chloroform (1 L). Next, the reaction mixture was washed with water and saturated sodium bicarbonate and then dried over sodium sulfate. The drying agent and solvent were removed to obtain crude 2,4,6-tri-O-acetyl-3-O-benzyl-α-D-glucosyl bromide. The product was used in the next step without further purification. Additional information about this step appears in Journal of Organic Chemistry, 1962, 3089-3092. The entire article is incorporated herein by reference.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][C@H:12]2[CH2:26][C@H:25]3[C@@H:15]([CH2:16][C:17]4[C:27]5[C:20](=[CH:21][CH:22]=[CH:23][C:24]3=5)[NH:19][CH:18]=4)[N:14]([CH3:28])[CH2:13]2)=[S:10])=C[CH:3]=1.C([C@@H]([C@H](C([O-])=O)O)O)([O-])=O>>[CH3:28][N:14]1[C@H:15]2[C@@H:25]([C:24]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:27]=3[C:17]([CH2:16]2)=[CH:18][NH:19]4)[CH2:26][C@H:12]([NH:11][C:9]([N:8]2[CH2:3][CH2:2][CH2:7][CH2:6][CH2:5]2)=[S:10])[CH2:13]1
Reactant: CN1C[C@@H](NC(=S)Nc2ccc(F)cc2)C[C@@H]2c3cccc4[nH]cc(c34)C[C@H]21
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Product: CN1C[C@@H](NC(=S)N2CCCCC2)C[C@@H]2c3cccc4[nH]cc(c34)C[C@H]21

Procedure:
1-(4-Fluorophenyl)-3-(6-methyl-8α-ergolinyl)thiourea, L-tartrate; 81% of theory; mp 260° C. (decomposition).
Reaction SMILES: [CH2:1]([O:5][CH:6]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:7][NH:8][CH2:9][CH:10]1[O:14][CH:13]([CH3:15])[CH:12]([CH3:16])[O:11]1)[CH2:2][CH2:3][CH3:4].C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:34][CH2:35][C:36](Cl)=[O:37]>O>[CH2:18]([O:17][CH:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH2:7][N:8]([CH2:9][CH:10]1[O:14][CH:13]([CH3:15])[CH:12]([CH3:16])[O:11]1)[C:36](=[O:37])[CH2:35][Cl:34])[CH2:19][CH2:20][CH3:21]
Reactant: CCCCOC(CNCC1OC(C)C(C)O1)OCCCC
Reactant: O=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CCCCOC(CN(CC1OC(C)C(C)O1)C(=O)CCl)OCCCC

Procedure:
N-(2,2-Dibutoxyethyl)-N-(4,5-dimethyl-1,3-dioxolan-2-ylmethyl)amine (0.05 mole), benzene (100 ml), water (100 ml) and sodium carbonate (2 grams) are charged into a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is cooled to a temperature of from 5° to 10° C and chloroacetyl chloride (0.05 mole) is added dropwise with stirring. After the addition is completed stirring is continued until the reaction mixture has reached room temperature. After this time the organic phase is separated from the aqueous phase and is washed with water. The washed solution is then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under reduced pressure to yield the desired product N-(2,2-dibutoxyethyl)-N-(4,5-dimethyl-1,3-dioxolan-2-ylmethyl)-α-chloroacetamide as the residue.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20]Cl)=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[CH3:26][NH:27][CH2:28][CH:29]([C:31]1[CH:32]=[N+:33]([O-:37])[CH:34]=[CH:35][CH:36]=1)[OH:30].C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20][N:27]([CH2:28][CH:29]([OH:30])[C:31]4[CH:32]=[N+:33]([O-:37])[CH:34]=[CH:35][CH:36]=4)[CH3:26])=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1
Reactant: Cc1c(CCl)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Reactant: CNCC(O)c1ccc[n+]([O-])c1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1c(CN(C)CC(O)c2ccc[n+]([O-])c2)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Temperature: 25 °C
Reaction time: 20 h
Yield: 59.4 %

Procedure:
A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (135 mg, 0.342 mmol), 2-(methylamino)-1-(1-oxidopyridin-3-yl)ethanol (Preparation 86, 69 mg, 0.50 mmol) and diisopropylethylamine (89 μL, 0.51 mmol) in dry DMF (5.0 mL) was stirred for 20 hours at room temperature. The solution was then diluted with water (20 mL). The resulting precipitate was collected by filtration and the collected solid was dried in vacuo, providing 107 mg of the titled compound as a white solid.