Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]([C@@:6]([C:21](=[O:23])[CH3:22])([C@:8]([C:18](=[O:20])[CH3:19])([C@:10]([C:15](=[O:17])[CH3:16])([C@@H:12]([CH3:14])[OH:13])[OH:11])[OH:9])[OH:7])=[O:5])(=[O:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=1.B(F)(F)F.CCOCC>ClCCl>[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C@:15]2([CH3:16])[O:17][C@:4]([C:1](=[O:3])[CH3:2])([OH:5])[C@:6]([C:21](=[O:23])[CH3:22])([OH:7])[C@@:8]([C:18](=[O:20])[CH3:19])([OH:9])[C@@:10]2([C:12](=[O:13])[CH3:14])[OH:11])=[CH:28][CH:27]=1
Reactant: COc1ccc(O)cc1
Reactant: CC(=O)C(=O)[C@@](O)(C(C)=O)[C@](O)(C(C)=O)[C@](O)(C(C)=O)[C@@H](C)O
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: COc1ccc([C@]2(C)O[C@@](O)(C(C)=O)[C@@](O)(C(C)=O)[C@](O)(C(C)=O)[C@]2(O)C(C)=O)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 63.7 %

Procedure:
D-Fucose (3) (4.95 g, 30.14 mmol) was dissolved in 30 mL of acetic anhydride and 30 mL of pyridine and stirred for 12 h. The solvent was removed in vacuo. Column chromatography (2:1 hexane/EtOAc) yielded 10.15 g (quant.) of 1,2,3,4-tetraacetyl-D-fucose (as a mixture of α-and β-anomer). 1,2,3,4-tetraacetyl-D-fucose (20.0 g, 60.2 mmol) and p-methoxyphenol (MPOH) (10.46 g, 84.3 mmol) were dissolved in 220 mL of dichloromethane and cooled to 0° C. BF3.OEt2 (21.4 g, 19.0 mL, 150.5 mmol) was added and the mixture stirred overnight. The reaction mixture was quenched by addition of saturated NaHCO3 solution, washed 2 times with water, dried over Na2SO4, concentrated and the residue was purified by column chromatography (3:1 hexane/EtOAc) yielding 16.8 g (71%) of 4-methoxyphenyl 1,2,3,4tetraacetyl-α-D-fucose (Only the β-anomer reacts, α-anomer could be recovered). 4-methoxyphenyl 1,2,3,4-tetraacetyl-α-D-fucose (3.90 g, 9.85 mmol) was dissolved in 150 mL of methanol and 6 mL of 0.5 M NaOMe solution were added. The mixture was stirred for 6 h. The solvent was removed in vacuo. Column chromatography (3:1 dichloromethane/methanol) afforded 2.63 g (99%) as a colorless solid: [α]D: +201.6 (c=0.32, CH3OH). 1H NMR (CD3OD, 300 MHz) δ 1.18 (d, J=6.6 Hz, 3H), 3.74 (s, 3H), 3.89 (m, 2H), 4.09 (quart., J=6.0 Hz, 1H), 5.31 (d, J=3.6 Hz, 1H), 6.82 (d, J=9.3 Hz, 2H), 7.04 (d, J=9.3 Hz, 2H). 13C NMR (CD3OD, 75 MHz) 16.3, 55.7, 67.9, 69.5, 71.2, 73.2, 100.0, 115.1, 119.0, 152.2, 156.0. MALDI-HRMS: m/z [M+Na]+ calcd 293.0996, obsd 293.0994.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@H:12]2[C@@H:16]3[O:17]C(C)(C)[O:19][C@@H:15]3[C@@H:14]([C:22]([NH:24][CH2:25][CH3:26])=[O:23])[O:13]2)=[C:5]([NH:27][CH2:28][CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:4]=1.C(N(CC)CC)C.[CH:49]1[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH:52]=[CH:51][C:50]=1[S:59](Cl)(=[O:61])=[O:60]>ClCCl>[C:36]1([CH:29]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:28][NH:27][C:5]2[N:4]=[C:3]([CH2:2][NH:1][S:59]([C:50]3[CH:51]=[CH:52][C:53]4[C:58](=[CH:57][CH:56]=[CH:55][CH:54]=4)[CH:49]=3)(=[O:61])=[O:60])[N:11]=[C:10]3[C:6]=2[N:7]=[CH:8][N:9]3[C@@H:12]2[O:13][C@H:14]([C:22]([NH:24][CH2:25][CH3:26])=[O:23])[C@@H:15]([OH:19])[C@H:16]2[OH:17])[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@@H]2OC(C)(C)O[C@@H]21
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CNS(=O)(=O)c4ccc5ccccc5c4)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 49.7 %

Procedure:
A solution of (3aS,4S,6R,6aR)-6-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide (Preparation 10) (140 mg, 0.25 mmol) and triethylamine (0.05 ml, 0.36 mmol) in anhydrous dichloromethane (1 ml) was treated with a solution of 2-naphthalenesulfonyl chloride (63 mg, 0.28 mmol) in anhydrous dichloromethane (1 ml). The mixture was stirred at room temperature for 18 hours during which time the solvent was allowed to evaporate off freely. The residue was dissolved in ethanol (1 ml), treated with hydrochloric acid (1M, 1 ml) and heated at 60° C. for 15 hours. The solvent was removed under reduced pressure and the residue was azeotroped with ethanol (×2). The residue was then purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (95:5 by volume) gradually changing to dichloromethane:methanol (90:10 by volume) to give a solid which was triturated with diethyl ether, diluted with pentane, filtered and dried to afford the title compound as a solid (88 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=O)[CH:7]([CH2:13][C:14](=O)[CH3:15])[CH2:6]2.O.[NH2:18][CH2:19][CH:20]([OH:22])[CH3:21]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8]1[N:18]([CH2:19][CH:20]([OH:22])[CH3:21])[C:14]([CH3:15])=[CH:13][C:7]=1[CH2:6]2
Reactant: CC(O)CN
Reactant: COc1ccc2c(c1)CC(CC(C)=O)C2=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc2c(c1)Cc1cc(C)n(CC(C)O)c1-2
Reaction time: 3 h
Yield: 82.7 %

Procedure:
A solution of 1.2 g of (RS)-5-methoxy-2-(2-oxopropyl)-1-indanone and 60 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated on a water separator. A solution of 1.65 g of (RS)-1-amino-2-propanol in 20 ml of anhydrous toluene was added dropwise to the boiling solution over a period of 5 minutes. Subsequently, the mixture was boiled for an additional 3 hours, during which the solvent was reduced to a volume of 30 ml. The cold reaction mixture was purified by column chromatography on silica gel (diethyl ether/hexane 7:3). 1.17 g (82%) of (RS)-1-(6-methoxy-2-methyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol were obtained as an oil.
Reaction SMILES: [S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Na+:6].[Na+].[S:8](=[O:11])(=[O:10])=[O:9].S([O-])(O)(=O)=O.[Na+]>O>[S:1]([O:5][S:8]([O-:11])(=[O:10])=[O:9])([O-:4])(=[O:3])=[O:2].[Na+:6].[Na+:6]
Reactant: O=S(=O)=O
Reactant: O=S(=O)([O-])[O-]
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Product: O=S(=O)([O-])OS(=O)(=O)[O-]

Procedure:
As the gaseous and solid streams flow counter current to each other, they undergo the reactions shown in equations 3 and 6. Beginning at the far right, the combustion gases are sufficiently hot to decompose sodium pyrosulfate to produce sodium sulfate and sulfur trioxide. The sodium sulfate is discharged from the kiln through a port at the far right end, and the sulfur trioxide enters the gas stream which is moving to the left. Somewhere towards the middle of the kiln, sodium hydrogen sulfate is decomposed to give sodium pyrosulfate and water vapor. The solid pyrosulfate moves toward the right while the water vapor flows with the combustion gases upwards towards the left. In the left hand section of the kiln, water vapor and sulfur trioxide combine to form sulfuric acid. This acid for the most part is lost with the product gases since the temperature of the flue gases at the exit exceeds the boiling points of lower concentrations of sulfuric acid. Acid in the feed combines with the salt to form hydrogen chloride and sodium hydrogen sulfate. The solid sodium hydrogen sulfate moves to the right while the hydrogen chloride escapes with the combustion gases through the vent in the left end of the kiln.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH:8]2[CH2:16][CH2:15][CH2:14][C:13]3[NH:12][CH:11]=[CH:10][C:9]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.O=P(Cl)(Cl)Cl.CN([CH:25]=[O:26])C>>[N:1]1([CH2:6][CH2:7][CH:8]2[CH2:16][CH2:15][CH2:14][C:13]3[NH:12][C:11]([CH:25]=[O:26])=[CH:10][C:9]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN(C)C=O
Reactant: c1cc2c([nH]1)CCCC2CCN1CCCC1
Solvent: O=P(Cl)(Cl)Cl
Product: O=Cc1cc2c([nH]1)CCCC2CCN1CCCC1

Procedure:
4-(2-Pyrrolidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-indole (475 mg, 2.2 mmol) was formylated with POCl3 (0.25 mL, 1.2 eq.) and DMF (2 ml) using standard Vilsmierer condition to give 250 mg of 4-(2-pyrrolidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde as alight yellow solid.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[F:5][C:6]1[CH:7]=[C:8]([N:18]2[CH2:22][C@H:21]([CH2:23][NH:24][C:25](=[O:27])[CH3:26])[O:20][C:19]2=[O:28])[CH:9]=[CH:10][C:11]=1[N:12]1[CH2:17][CH:16]2[CH:14]([O:15]2)[CH2:13]1>CC(C)=O.O>[N:1]([CH:16]1[CH:14]([OH:15])[CH2:13][N:12]([C:11]2[CH:10]=[CH:9][C:8]([N:18]3[CH2:22][C@H:21]([CH2:23][NH:24][C:25](=[O:27])[CH3:26])[O:20][C:19]3=[O:28])=[CH:7][C:6]=2[F:5])[CH2:17]1)=[N+:2]=[N-:3]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CC4OC4C3)c(F)c2)C(=O)O1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CC(O)C(N=[N+]=[N-])C3)c(F)c2)C(=O)O1
Temperature: 55 °C

Procedure:
Sodium azide (42 mg, 0.64 mmol) was added to a solution of N-({(5S)-3-[3-fluoro-4-(6-oxa-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (36 mg, 0.107 mmol, prepared using the general procedure described for Example 40) in 2:1 acetone-H2O (1.0 mL) and the solution heated at 55° C. for 16 hours. The solution was cooled, concentrated to remove acetone, diluted with water and extracted with chloroform. Combined organic extracts were dried (MgSO4), filtered and concentrated to provide the title compound. This material was used directly in the next reaction. MS (m/z): [M+H]+=379
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@H:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])#[N:2].Cl.[NH2:21][OH:22]>CCO>[OH:22][NH:21][C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@H:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[NH:2]
Reactant: NO
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCc2c(C#N)cccc21
Agent: Cl
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H]1CCc2c(C(=N)NO)cccc21
Temperature: 85 °C
Yield: 85 %

Procedure:
Prepared using General Procedure 1. To (R)-tert-butyl 4-cyano-2,3-dihydro-1H-inden-1-ylcarbamate INT-52 (15.0 g, 58.2 mmol) in EtOH (100 mL) was added hydroxylamine hydrochloride (12.1 g, 174.2 mmol) and TEA (17.6 mL, 174.2 mmol) and the reaction mixture was heated at 85° C. for 2 h. The solvents were removed and the resulting white solid was partitioned between water and DCM. The organic layers were dried over Na2SO4, concentrated, and recrystallized from isopropanol (50 mL) to afford 14.4 g (85%) of (R)-tert-butyl 4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-54 as white crystalline solid. LCMS-ESI (m/z) calculated for C15H21N3O3: 291.4; found 292.1 [M+H]+, tR=2.04 min. 1H NMR (400 MHz, DMSO) δ 9.53 (s, 1H), 7.38-7.32 (m, 1H), 7.32-7.12 (m, 3H), 5.68 (s, 2H), 4.97 (q, J=8.5, 1H), 3.07 (ddd, J=16.6, 8.7, 2.6, 1H), 2.86 (dt, J=16.8, 8.4, 1H), 2.30 (ddd, J=12.6, 7.6, 3.6, 1H), 1.75 (dq, J=12.3, 9.0, 1H), 1.44 (s, 9H).
Reaction SMILES: O1CCCC1.[NH2:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[C:9]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[N:8]=1.[C:27](Cl)(=[O:33])[CH:28]=[CH:29][CH:30]=[CH:31][CH3:32]>C(N(CC)CC)C>[NH2:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[C:9]([N:21]2[CH2:26][CH2:25][N:24]([C:27](=[O:33])[CH:28]=[CH:29][CH:30]=[CH:31][CH3:32])[CH2:23][CH2:22]2)[N:8]=1
Reactant: CC=CC=CC(=O)Cl
Reactant: COc1cc2nc(N3CCNCC3)nc(N)c2cc1OC
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC=CC=CC(=O)N1CCN(c2nc(N)c3cc(OC)c(OC)cc3n2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 85.1 %

Procedure:
To 20 ml of tetrahydrofuran were added 1.16 g of 4-amino-6,7-dimethoxy-2-(1-piperazinyl)quinazoline and 1.5 g of triethylamine. There was then added 0.52 g of 2,4-hexadienoyl chloride, after which the mixture was stirred at room temperature for 3 hours. The reaction mixture was then concentrated by evaporation under reduced pressure, and the resulting residue was washed with water and recrystallized from ethanol, to give 1.3 g of the desired Compound No. 10 in the form of pale yellow powdery crystals melting at 231°-233° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:25])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[CH3:26][C:27]1([CH3:43])[O:32][CH:31]([C:33]([NH:35][CH2:36][CH2:37][C:38](O)=[O:39])=[O:34])[C:30]([CH3:42])([CH3:41])[CH2:29][O:28]1>>[C:7]([NH:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:38](=[O:39])[CH2:37][CH2:36][NH:35][C:33]([CH:31]1[C:30]([CH3:41])([CH3:42])[CH2:29][O:28][C:27]([CH3:43])([CH3:26])[O:32]1)=[O:34])(=[O:25])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)NCCCCN
Reactant: CC1(C)OCC(C)(C)C(C(=O)NCCC(=O)O)O1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)NCCCCNC(=O)CCNC(=O)C1OC(C)(C)OCC1(C)C
Yield: 44.8 %

Procedure:
N-(4-Aminobutyl)oleamide (3.77 g) and 2.59 g of 3-[N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionic acid were reacted in the same manner as in Example 1 to obtain 2.66 g of the title compound (yield: 45%).
Reaction SMILES: CC1(C)[O:6][C:5](=[O:7])[CH:4]([CH:8]([CH2:12][CH2:13][CH2:14][CH3:15])[C:9]([OH:11])=O)[O:3]1.[NH:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1>>[OH:3][C@@H:4]([C@H:8]([C:9]([N:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)=[O:11])[CH2:12][CH2:13][CH2:14][CH3:15])[C:5]([OH:6])=[O:7]
Reactant: c1ccc(C2CCCN2)nc1
Reactant: CCCCC(C(=O)O)C1OC(C)(C)OC1=O
Product: CCCC[C@@H](C(=O)N1CCCC1c1ccccn1)[C@H](O)C(=O)O

Procedure:
The title compound is prepared from 2-(2,2-dimethyl-4-oxo-1,3-dioxolan-5-yl)hexanoic acid B-5 and commercially available 2-pyrrolidin-2-yl-pyridine A-5 according to General Procedure B.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[Cl:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[Cl:25])[CH:21]([CH3:26])[NH:20][CH2:19][CH2:18]2>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:20]3[CH2:19][CH2:18][C:17]4[C:22](=[CH:23][C:24]([Cl:25])=[C:15]([Cl:14])[CH:16]=4)[CH:21]3[CH3:26])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: CC1NCCc2cc(Cl)c(Cl)cc21
Reactant: O=C(O)c1cc2ncc(Cl)cn2n1
Product: CC1c2cc(Cl)c(Cl)cc2CCN1C(=O)c1cc2ncc(Cl)cn2n1

Procedure:
In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 6,7-dichloro-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[O:9][CH3:10].CCN(CC)CC.[F:18][C:19]1([F:34])[O:23][C:22]2[CH:24]=[CH:25][C:26]([C:28]3([C:31](Cl)=[O:32])[CH2:30][CH2:29]3)=[CH:27][C:21]=2[O:20]1>ClCCl>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:31]([C:28]2([C:26]3[CH:25]=[CH:24][C:22]4[O:23][C:19]([F:34])([F:18])[O:20][C:21]=4[CH:27]=3)[CH2:30][CH2:29]2)=[O:32])[CH:5]=[CH:4][C:3]=1[O:9][CH3:10]
Reactant: O=C(Cl)C1(c2ccc3c(c2)OC(F)(F)O3)CC1
Reactant: COc1ccc(N)nc1Br
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Br
Temperature: 25 °C
Reaction time: 18 h
Yield: 79.6 %

Procedure:
To a solution of 6-bromo-5-methoxypyridin-2-amine (510 mg, 2.5 mmol) and Et3N (690 μL, 4.9 mmol) in dichloromethane (10 mL) was added a solution of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (650 mg, 2.5 mmol) in dichloromethane (5 mL). The resulting reaction mixture was allowed to stir at room temperature for 18 hours. The reaction mixture was then washed with 1N HCl (1×20 mL) and saturated aqueous NaHCO3 (1×20 mL). The organics were dried over sodium sulfate and evaporated to yield the product (850 mg, 81%). ESI-MS m/z calc. 426.0, found 427.3 (M+1)+. Retention time 2.05 minutes.
Reaction SMILES: [NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][N:8]=2)[CH2:3]1.[C:14]([O:18][C:19]([NH:21][C:22]([NH:24][CH2:25][CH3:26])=S)=[O:20])([CH3:17])([CH3:16])[CH3:15].Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(OCC)(=O)C>[C:14]([O:18][C:19]([NH:21][C:22]([NH:24][CH2:25][CH3:26])=[N:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][N:8]=2)[CH2:3]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: CCNC(=S)NC(=O)OC(C)(C)C
Reactant: Cc1ccnc(N2CCC(N)C2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCNC(=NC1CCN(c2cc(C)ccn2)C1)NC(=O)OC(C)(C)C
Reaction time: 18 h
Yield: 83.6 %

Procedure:
To a solution of 3-amino-1-(4-methylpyridin-2-yl)pyrrolidine (177 mg) and N-(tert-butoxycarbonyl)-N′-ethylthiourea (245 mg) in N,N-dimethylformamide (5 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (230 mg), and the mixture was stirred for 18 hours. The mixture was diluted with ethyl acetate, washed with water three times and brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 25 g, 5% methanol in dichloromethane) to give N-(tert-butoxycarbonyl)-N′-ethyl-N″-(1-(4-methylpyridin-2-yl)-pyrrolidin-3-yl)guanidine (290 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([CH2:15][CH2:16][CH2:17][CH2:18][CH:19](O)[CH:20]=[CH:21][C:22]3[CH:23]=[N:24][C:25]([CH3:28])=[N:26][CH:27]=3)[CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C(O)(=O)CC.Cl.[Cl-].[Na+].O.[C:41]([CH3:51])(OCC)([O:45]CC)[O:42][CH2:43][CH3:44]>>[CH2:43]([O:42][C:41](=[O:45])[CH2:51][CH:21]([C:22]1[CH:23]=[N:24][C:25]([CH3:28])=[N:26][CH:27]=1)[CH:20]=[CH:19][CH2:18][CH2:17][CH2:16][CH2:15][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:8][CH2:7][C:6]2[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:14]=1)[CH3:44]
Reactant: CCOC(C)(OCC)OCC
Reactant: COc1ccc(CNc2cccc(CCCCC(O)C=Cc3cnc(C)nc3)n2)cc1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CCC(=O)O
Solvent: O
Product: CCOC(=O)CC(C=CCCCCc1cccc(NCc2ccc(OC)cc2)n1)c1cnc(C)nc1
Temperature: 25 °C
Yield: 86 %

Procedure:
A solution of the allylic alcohol 16-4 (2.3 g, 5.49 mmol) in (EtO)3CMe (10 mL) was treated with 100 uL of a 1 mL solution of (EtO)3CMe containing 10 uL of propionic acid. The yellow solution was heated at 150° for 90 minutes. The solution was cooled to room temperature and poured into 1N HCl/brine. The mixture was extracted with CHCl3, dried, concentrated, and purified on silica gel (90:5:5 CHCl3:EtOAc:MeOH) to give 2.32 g (86%) of 16-7.
Reaction SMILES: [CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:40])[C@@H:24]([NH:31][C:32]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6].[C:63]1(=[O:69])[O:68][C:66](=[O:67])[CH2:65][CH2:64]1.O>N1C=CC=CC=1>[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([O:40][C:63]([CH2:64][CH2:65][C:66]([OH:68])=[O:67])=[O:69])[C@@H:24]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6]
Reactant: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reactant: O=C1CCC(=O)O1
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](OC(=O)CCC(=O)O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reaction time: 3 h

Procedure:
After 3 hours at room temperature, a solution of 500 mg (0.59 mmole) of taxol, 900 mg (7.6 mmole) of succinic anhydride in 12 mL of pyridine is evaporated to dryness in vacuo. The residue is treated with 20 mL of water, stirred for 20 min. and filtered. The precipitate is dissolved in acetone, water slowly added, and the fine crystals collected. This yields 490 mg (86%) of title compound which showed: mp 178°-80° C.; [a] -42.1° (c=1.1 EtOH); Anal. (C H NO H O) C,H,N.
Reaction SMILES: [CH2:1]([C:3](C)=O)[CH3:2].[N:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>>[CH2:11]([NH2:6])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:2][CH2:1][CH3:3]
Reactant: c1ccncc1
Reactant: CCC(C)=O
Product: CCCCCCCCN
Yield: 489.6 %

Procedure:
A mixture of 20.4 g of the white solid obtained in Intermediate Preparation Example 8, 6.4 g of n-octylamine, 80 g of methyl ethyl ketone and 0.8 g of pyridine was heated at a temperature of 70° C. and reacted with stirring for 10 hours. After cooling, the reaction mixture was added in 800 mL of methanol with stirring over 15 minutes, and the mixture was further stirred for one hour. A deposited solid was collected by filtration and dried in vacuo to obtain 28 g of a pale whitish yellow solid. The resulting compound had a molecular weight measured by high-performance liquid chromatography of 15,000.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=2)[O:7][N:6]=1)=[O:4].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:39][CH:40]([OH:43])[CH:41]=[CH2:42].C(N(CC)CC)C>CN(C)C=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH2:42][CH2:41][C:40](=[O:43])[CH3:39])[CH:11]=2)[O:7][N:6]=1)=[O:4]
Reactant: C=CC(C)O
Reactant: COC(=O)c1cc(-c2cccc(Br)c2)on1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(-c2cccc(CCC(C)=O)c2)on1
Temperature: 100 °C
Yield: 59.4 %

Procedure:
To a mixture of 5-(3-Bromo-phenyl)-isoxazole-3-carboxylic acid methyl ester (1.5 g, 5.3 mmol), Pd(OAc)2 (60 mg, 0.27 mmol), P(o-tolyl)3 (162 mg, 0.53 mmol) in anhydrous N,N-dimethylformamide (15 mL) in a pressure tube was added 3-buten-2-ol (0.92 mL, 10.6 mmol) and triethylamine (1.1 mL, 7.95 mmol). The mixture was flushed with nitrogen for 3 minutes, capped and heated to 100° C. for 30 minutes. The reaction mixture was allowed to cool to ambient temperature, partitioned between ethyl acetate and water (75 mL, 1:1). The organic layer was washed with brine (2×25 mL), dried (Na2SO4), filtered, concentrated under reduced pressure and purified on a Silica Gel MPLC eluting with 20–40% ethyl acetate/hexanes to provide the titled compound as a light yellow solid (860 mg, 59%). MS (ESI(+)) m/e 274 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:5]([CH3:13])[N:4]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23](=O)[O:24]C3C=CC=CC=3)=[CH:16][CH:15]=2)[N:3]=1.[CH3:32][N:33]([CH3:47])[CH2:34][CH2:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([S:43]([NH2:46])(=[O:45])=[O:44])=[CH:39][CH:38]=1>>[CH3:32][N:33]([CH3:47])[CH2:34][CH2:35][O:36][C:37]1[CH:38]=[CH:39][C:40]([S:43]([NH:46][C:23]([NH:22][CH2:21][CH2:20][C:17]2[CH:16]=[CH:15][C:14]([N:4]3[C:5]([CH3:13])=[C:6]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:2]([CH3:1])=[N:3]3)=[CH:19][CH:18]=2)=[O:24])(=[O:45])=[O:44])=[CH:41][CH:42]=1
Reactant: Cc1nn(-c2ccc(CCNC(=O)Oc3ccccc3)cc2)c(C)c1-c1ccccc1
Reactant: CN(C)CCOc1ccc(S(N)(=O)=O)cc1
Product: Cc1nn(-c2ccc(CCNC(=O)NS(=O)(=O)c3ccc(OCCN(C)C)cc3)cc2)c(C)c1-c1ccccc1

Procedure:
The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 4-[2-(dimethylamino)ethoxy]benzenesulfonamide: 1H-NMR [CDCl3/CD3OD(4:1)] δ δ 7.87-7.84 (2H, m), 7.48-7.26 (9H, m), 7.01-6.98 (2H, m), 4.19-4.15 (2H, m), 3.46-3.41 (2H, m), 2.92-2.82 (4H, m), 2.45 (6H, s), 2.32 (3H, s), 2.27 (3H, s).