Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: NC(=O)[C@@H:3]([NH:8][C:9](=[O:37])[C@@H:10]([NH:15][C:16]([N:18]1[C:26]2[CH2:25][CH2:24][N:23]([CH3:27])[CH2:22][C:21]=2[C:20]([C:28]2[CH:33]=[C:32]([F:34])[C:31]([F:35])=[CH:30][C:29]=2[F:36])=[N:19]1)=[O:17])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH:5](C)C.NCCC[OH:43]>>[OH:43][CH2:5][CH2:4][CH2:3][NH:8][C:9](=[O:37])[C@@H:10]([NH:15][C:16]([N:18]1[C:26]2[CH2:25][CH2:24][N:23]([CH3:27])[CH2:22][C:21]=2[C:20]([C:28]2[CH:33]=[C:32]([F:34])[C:31]([F:35])=[CH:30][C:29]=2[F:36])=[N:19]1)=[O:17])[C:11]([CH3:13])([CH3:12])[CH3:14]
Reactant: NCCCO
Reactant: CC(C)C[C@H](NC(=O)[C@@H](NC(=O)n1nc(-c2cc(F)c(F)cc2F)c2c1CCN(C)C2)C(C)(C)C)C(N)=O
Product: CN1CCc2c(c(-c3cc(F)c(F)cc3F)nn2C(=O)N[C@H](C(=O)NCCCO)C(C)(C)C)C1

Procedure:
Compound 80 was prepared according to the procedure described for the synthesis of compound 72 by replacing leucine amide with 3-amino-propan-1-ol. LCMS (+ESI) m/z=482.3 [M+H]+.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][C:11]([C:15](=[O:27])[NH:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[O:23][CH2:24][CH2:25][O:26][C:18]=23)([OH:14])[CH2:10][CH2:9]1)(C)(C)C.CO>C(OCC)(=O)C>[O:26]1[C:18]2[C:19](=[N:20][CH:21]=[CH:22][C:17]=2[NH:16][C:15]([C:11]2([OH:14])[CH2:12][CH2:13][CH:8]([NH2:7])[CH2:9][CH2:10]2)=[O:27])[O:23][CH2:24][CH2:25]1
Reactant: CC(C)(C)OC(=O)NC1CCC(O)(C(=O)Nc2ccnc3c2OCCO3)CC1
Solvent: CCOC(C)=O
Solvent: CO
Product: NC1CCC(O)(C(=O)Nc2ccnc3c2OCCO3)CC1
Yield: 31.9 %

Procedure:
This was prepared from carbamate (b) (105 mg) by the procedure of Example (1m) with the exception that the crude material was subjected to chromatography on silica eluting with a 0-30% methanol in ethyl acetate gradient affording an oil (25 mg, 32%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:3]=12.[Br:14]N1C(=O)CCC1=O.O>C(O)(=O)C>[Br:14][C:7]1[C:2]([Cl:1])=[C:3]2[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][NH:8][C:4]2=[N:5][CH:6]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: O=[N+]([O-])c1c[nH]c2nccc(Cl)c12
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1c[nH]c2ncc(Br)c(Cl)c12
Temperature: 25 °C
Reaction time: 18 h
Yield: 64.2 %

Procedure:
Into a suspension of 4-chloro-3-nitro-1H-pyrrolo[2,3-b]pyridine (50.0 g) in acetic acid (300 mL) were added N-bromosuccinimide (NBS, 70.9 g, 1.60 equiv) in small portions at 25° C. The reaction mixture was stirred at 25° C. for 18 h. Water (3.0 mL) was added slowly over 30 min to get a light yellow slurry. The resulting solid was collected by filtration and washed with a 2:2:1 (v/v/v) mixture of saturated sodium sulfite solution, water, and methanol, followed by water and a 1:1 (v/v) mixture of methanol and water. The cake was dried in a vacuum at 50° C. oven overnight to give the 44.9 g (65% yield) of 5-bromo-4-chloro-3-nitro-1H-pyrrolo[2,3-b]pyridine as an light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 13.7 (s, 1H), 8.93 (s, 1H), 8.66 (s, 1H). 13C NMR (75 MHz, DMSO-d6) δ 146.9, 146.4, 133.9, 133.2, 127.0, 116.7, 111.3. HRMS calcd. For C7H2BrC1N3O2 [M-H]−: 273.9024, found 273.9031.
Reaction SMILES: Cl[S:2]([C:5]1[S:6][C:7]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3].[NH2:19][C:20]1[O:24][N:23]=[C:22]([CH3:25])[C:21]=1[Br:26]>>[Br:26][C:21]1[C:22]([CH3:25])=[N:23][O:24][C:20]=1[NH:19][S:2]([C:5]1[S:6][C:7]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3]
Reactant: O=S(=O)(Cl)c1ccc(COCc2ccccc2)s1
Reactant: Cc1noc(N)c1Br
Product: Cc1noc(NS(=O)(=O)c2ccc(COCc3ccccc3)s2)c1Br
Yield: 31.2 %

Procedure:
N-(4-Bromo-3-methyl-5-isoxazolyl)-5-(benzyloxymethyl)thiophene-2-sulfonamide was prepared as described in Example 10 from 2-chlorosulfonyl-5-(benzyloxymethyl)thiophene (520 mg, 1.72 mmol) and 5-amino-4-bromo-3-methyl isoxazole (319 mg, 1.8 mmol). Purification by column chromatography using 10% MeOH/CHCl3 gave 238 mg of pure N-(4-bromo-3-methyl-5-isoxazolyl)-5-(benzyloxymethyl)thiophene-2-sulfonamide as brown semisolid (31 % yield, m.p. 92° C.).
Reaction SMILES: [CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([CH:16]=[C:17]([C:32]#[N:33])[C:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2].[C-:34]#[N:35].[Na+].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>CN(C)C=O.O.C(Cl)(Cl)Cl>[CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]([C:16]([C:34]#[N:35])=[C:17]([C:32]#[N:33])[C:18]3[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2]
Reactant: [C-]#N
Reactant: CCn1c2ccccc2c2cc(C=C(C#N)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)ccc21
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [Pb+4]
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: CCn1c2ccccc2c2cc(C(C#N)=C(C#N)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)ccc21
Reaction time: 0.17 h
Yield: 23.7 %

Procedure:
1.0 g (2.18 mmol) of N-ethyl-3-(2-cyano-2-(3,5-bis(trifluoromethyl)phenyl)ethenyl) carbazole and 10 ml of N,N-dimethylformamide as solvent were placed in a 200 ml four-necked flask with a mechanical stirrer and bulb-shaped cooler. To this was added an aqueous solution prepared from 0.11 g (2.25 mmol) of sodium cyanide and 1.0 ml of water, which was stirred for 10 minutes. Further, 1.0 g (2.25 mmol) of lead tetraacetate was added. The resultant product was subjected to the reaction for 30 minutes. After the reaction was completed, 100 ml of chloroform was added. To the resultant solution was added 50 ml of water. The resultant liquid was washed in a separatory funnel. To the washed liquid was added sodium sulfate, which was left to stand for 30 minutes and dehydrated. The dehydrated solution was concentrated in an evaporator and dried under vacuum to obtain 0.25 g of a brown solid. The yield of the synthesized compound was 24%, and its melting point was 180-182° C. The IR chart is shown in FIG. 19.
Reaction SMILES: [N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([NH:5][C@H](C(N)=O)C(C)C)=[O:4].Cl.[CH2:24]1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N([OH:48])N=NC=2C=1>>[N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([OH:4])=[O:48].[NH:1]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[C@H:2]([C:3]([NH2:5])=[O:4])[CH:13]([CH3:14])[CH3:24]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: On1nnc2ccccc21
Reactant: CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C(N)=O
Agent: Cl
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Product: CC(C)[C@H](NC(=O)OC(C)(C)C)C(N)=O

Procedure:
In such a synthesis, the lysine side chain is protected by a MSOC protective group introduced onto Boc-Lys-OH so as to form Boc-Lys(MSOC)-OH. The diprotected N(α),N(ε) lysine is coupled with Boc-Pro-Val-NH2, HCl by the conventional DCC/HOBt method. The Boc-Pro-Val-NH2, HCl reactant is in turn obtained in two steps from Boc-Pro-OH and Boc-Val-NH2. The overall yield is 33% calculated based on Boc-Lys(MSOC)-OH. The global synthesis scheme is illustrated in the scheme (I) hereunder:
Reaction SMILES: [C:1]([NH:11][C@H:12]([C:16]([OH:18])=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].ClC(N(C)C)=C(C)C.[CH2:27]([O:34][C:35]([C@:37]1([O:48][C@@H:47]([C@@H:49]([C@@H:51]([CH2:53]O)[OH:52])[OH:50])[C@H:42]([NH:43][C:44](=[O:46])[CH3:45])[C@@H:40]([OH:41])[CH2:39]1)[OH:38])=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl.N1C=CC=CC=1>[CH2:27]([O:34][C:35]([C:37]1([OH:38])[CH2:39][CH:40]([OH:41])[CH:42]([NH:43][C:44](=[O:46])[CH3:45])[CH:47]([CH:49]([OH:50])[CH:51]([OH:52])[CH2:53][O:17][C:16](=[O:18])[CH:12]([NH:11][C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[CH:13]([CH3:14])[CH3:15])[O:48]1)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@](O)(C(=O)OCc2ccccc2)C[C@@H]1O
Reactant: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: CC(C)=C(Cl)N(C)C
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)NC1C(O)CC(O)(C(=O)OCc2ccccc2)OC1C(O)C(O)COC(=O)C(NC(=O)OCc1ccccc1)C(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 32 %

Procedure:
To a solution of Carbobenzyloxy-L-Valine (1.35 g, 5.37 mmol) in anhydrous dichloromethane (12 mL) at 0° C. under argon is added 1-Chloro-N,N,-2-trimethyl-1-propenylamine (848 μL, 6.34 mmol) by dropwise addition via a syringe. The resulting solution is then stirred at 0° C. for 10 minutes resulting in a clear colorless solution. To this solution is then added the N-Acetyl-β-neuraminic Acid Benzyl ester (1-2), previously dissolved in anhydrous pyridine (8.0 mL) via dropwise addition. The solution immediately turns yellow and is kept at 0° C. and under an argon atmosphere for 3 hours. The cooling bath is then removed and the solution kept at rt for overnight resulting in a cloudy suspension. The solvents are removed under high vacuum being careful that the temperature bath does not exceed 50° C. to give a light yellow oil. In order to remove traces of pyridine, the oil is triturated with toluene and again evaporated under high vacuum. The remaining oil is dissolved in minimum amount of dichloromethane (DCM) and loaded directly unto a silica gel column (Silicycle-FLH-R10030B-ISO80, 80 g Cartridge) and purified by flash chromatography (Mobile Phase: DCM/Methanol=96/4 to 88/12 over 24 minutes). Combination of the purest fractions yields 996 mg (32% yield) of pure (1-5) as a white solid. LC/MS: (+) ESI: m/z=633.2 [M+1]; 655.2 [M+Na, major signal); retention time=3.69 min. 1H NMR (400 MHz, d4-MeOD) δ 7.12-7.37 (m, 11H), 5.08-5.17 (m, 2H), 4.95-5.03 (m, 2H), 4.28 (dd, J=11.6, 2.0 Hz, 1H, C-9), 4.18 (dd, J=11.6, 6.0 Hz, 1H, C-9′) 4.05-4.06 (m, 1H), 3.91-3.98 (m, 1H), 3.89 (dd, J=10.5, 1.2 Hz, 1H), 3.80-3.86 (m, 11H), 3.70 (t, 1H), 3.41-3.43 (m, 1H), 2.14 (dd, J=12.8, 4.8 Hz, 1H), 1.98-2.08 (m, 1H), 1.91 (s, 3H), 1.79-1.89 (m, 1H), 0.80-0.84 (m, 6H); 13C NMR (400 mHz, d4-MeOD) δ 173.7, 170.9, 158.9, 136.2, 137.1, 129.6, 129.5, 129.4, 129.1, 129.0, 128.8, 96.7, 72.0, 70.3, 69.3, 68.3, 68.0, 67.8, 61.1, 54.4, 40.7, 32.1, 22.7, 19.6, 18.4.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:14][NH2:15].O>C1COCC1>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:15][CH3:14])(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
Reactant: CN
Reactant: CC(=O)c1ccc(S(=O)(=O)Cl)cc1
Solvent: C1CCOC1
Solvent: O
Product: CNS(=O)(=O)c1ccc(C(C)=O)cc1
Reaction time: 0.5 h
Yield: 62.8 %

Procedure:
Ex-29A: To a solution of 4-acetylbenzenesulfonyl chloride (1.1 g, 5.0 mmol) in 25 ml of THF, methylamine (0.44 ml of 40% solution in H2O, 5 mmol) was added dropwise, and the mixture was stirred for 30 min. The reaction mixture was poured into water, and the precipitate was filtered. Recrystallization from EtOAc/hexanes gave 0.67 g (62.6%) of 4-acetyl-N-methyl-benzenesulfonamide as a white solid. 1H-NMR (300 MHz, CDCl3) δ 8.09 (d, J=8 Hz, 2H), 7.96 (d, J=8 Hz, 2H), 4.48 (br, 1H), 2.70 (d, J=4 Hz, 1H), 2.66 (s, 3H).
Reaction SMILES: [C:1]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O-:8])=[O:7].Br[CH2:19][Cl:20]>>[C:1]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:19][Cl:20])=[O:7]
Reactant: O=C([O-])CCCCC(=O)OCc1ccccc1
Reactant: ClCBr
Product: O=C(CCCCC(=O)OCc1ccccc1)OCCl
Temperature: 0 °C
Reaction time: 8 h
Yield: 48 %

Procedure:
To 350 ml of bromochloromethane cooled to 0° C. is added 67 g (0.14 mole) tetrabutylammonium salt of benzyl adipate half ester and the mixture is stirred overnight at 0° C. then allowed to warm to room temperature. The excess bromochloromethane is evaporated in vacuo, 400 ml ethyl ether is added to the residue and the mixture is stirred to form crystals of tetrabutylammonium bromide. The crystals are removed by filtration, washed with ether, stirred with ethyl acetate (300 ml) for one hour and refiltered and washed with ethyl acetate. The combined filtrates are evaporated in vacuo, the residue purified by chromatography on silica gel (1 kg), eluting with 2:1 hexane/ethyl acetate, to yield 19.1 g (48%) of the title compound. 1H-NMR (CDCl3) ppm (delta): 1.58-1.9 (m, 4H), 2.2-2.62 (n, 4H), 5.13 (s, 2H), 5.68 (s, 2H), 7.38 (s, 5H).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:18]([C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1)([O-:20])=[O:19]>>[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:29])[O:17][C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH2:10]3)=[CH:25][CH:26]=1)([O-:20])=[O:19]
Reactant: O=C=Nc1ccc([N+](=O)[O-])cc1
Reactant: Oc1ccc2c(c1)CCN2Cc1ccccc1
Product: O=C(Nc1ccc([N+](=O)[O-])cc1)Oc1ccc2c(c1)CCN2Cc1ccccc1

Procedure:
The title compound was synthesized from 1-benzylindolin-5-ol (70.0 mg, 0.311 mmol) using the same procedure employed for Example 2 (2), but with 4-nitrophenylisocyanate instead of 4-isopropylphenylisocyanate. The product was obtained as a slightly yellow solid (7.1 mg, 6%) having the following characteristics.
Reaction SMILES: [C:1]([C:4]1[S:5]C=C[CH:8]=1)(=O)[CH3:2].[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([CH2:16][C:17]#[N:18])=[O:15].N1CCOCC1.[S]>CC(=O)CC>[NH2:18][C:17]1[S:5][C:4]([CH3:8])=[C:1]([CH3:2])[C:16]=1[C:14]([C:10]1[S:9][CH:13]=[CH:12][CH:11]=1)=[O:15]
Reactant: N#CCC(=O)c1cccs1
Reactant: CC(=O)c1cccs1
Agent: [S]
Solvent: C1COCCN1
Solvent: CCC(C)=O
Product: Cc1sc(N)c(C(=O)c2cccs2)c1C
Yield: 44 %

Procedure:
The procedure of Example 1 was followed except that 2-acetylthiophene (Aldrich) was used in place of acetophenone to prepare the corresponding 2-(thiophene-2-carbonyl)acetonitrile (Steps A and B). 2-Butanone (Aldrich), 2-(thiophene-2-carbonyl)acetonitrile, morpholine, and sulfur were reacted according to the procedure of Step C, Example 1, to afford the desired compound. Yield: 44%; IR (KBr) cm−1: 3390, 3269, 1552, 1429, 1272, 852, 772; 1H NMR (CDCl3):δ 1.86 (s, 3H), 2.17 (s, 3H), 5.78(bs, 2H), 7.07 (dd, 1H, J=3.8 and 4.8 Hz), 7.56 (dd, 1H, J=2.8 and 0.8 Hz), 7.58 (dd, 1H, J=5.0 and 0.8 Hz); orange solid, mp: 117–118° C. (petroleum ether).
Reaction SMILES: [S:1]1[CH:5]=[C:4]([C:6](=O)[C:7]([OH:9])=[O:8])[CH:3]=[N:2]1.[OH-:11].[Mg+2].[OH-].Cl.[NH2:15]O>C(O)C.O>[OH:11][N:15]=[C:6]([C:4]1[CH:3]=[N:2][S:1][CH:5]=1)[C:7]([OH:9])=[O:8]
Reactant: O=C(O)C(=O)c1cnsc1
Reactant: NO
Reactant: [OH-]
Agent: Cl
Agent: [Mg+2]
Solvent: O
Solvent: CCO
Product: O=C(O)C(=NO)c1cnsc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 76.1 %

Procedure:
A suspension of 2-(isothiazol-4-yl)glyoxylic acid (240 mg.), magnesium hydroxide (290 mg.) and hydroxylamine hydrochloride (140 mg.) in a mixture of ethanol (2 ml.) and water (10 ml.) was stirred for 2 hours at ambient temperature and allowed to stand overnight at ambient temperature. Ethanol was distilled off and to the residue was added ethyl acetate. The mixture was adjusted to pH 1 with 10% hydrochloric acid and the ethyl acetate layer was washed with water and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give 2-hydroxyimino-2-(isothiazol-4-yl)acetic acid (syn isomer) (0.20 g.), mp 159° to 161° C. (dec.).
Reaction SMILES: C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O.[CH2:22]([O:29][C@H:30]1[C@H:35]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@H:34]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@H:33]([CH3:52])[O:32][C@@H:31]1[O:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][OH:64])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(Cl)Cl.S(=O)(=O)(O)O>C(O)C>[CH2:22]([O:29][C@H:30]1[C@H:35]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@H:34]([O:44][CH2:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[C@H:33]([CH3:52])[O:32][C@@H:31]1[O:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH:63]=[O:64])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: C[C@@H]1O[C@H](OCCCCCCCCCCO)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCO
Product: C[C@@H]1O[C@H](OCCCCCCCCCC=O)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 71 %

Procedure:
PDC oxidation of 10-(2,3,4-tri-O-benzyl-β-L-fucopyranosyloxy)-n-decanol. Under an atmosphere of nitrogen, pyridinium dichromate (550 mg, 1.424 mmol) was added to a dry methylene chloride solution (20 mL) of 10-(2,3,4-tri-O-benzyl-β-L-fucopyranosyloxy)-n-decanol (580 mg, 0.982 mmol). The resulting brown slurry was stirred at room temperature under nitrogen. TLC analysis (visualization by UV and char with 10% sulfuric acid in ethanol) of the reaction mixture indicated complete consumption of the starting material and the formation of a new compound after 18 h. The reaction mixture was treated with ether (10 mL), filtered through silica gel and Celite with an ether wash (25 mL) and concentrated to an off-white oil. Chromatographic purification (silica gel, 20% ethyl acetate in hexanes) afforded 410 mg (0.697 mmol, 71%) of 10-(2,3,4-tri-O-benzyl-β-L-fucopyranosyloxy)-n-decanal as a clear oil. Rf =0.50 (silica gel, 30% ethyl acetate in hexanes); 1H NMR (CDCl3, 300 MHz) δ: 9.76 (t, J=1.8 Hz, 1H), 7.35 (m, 15H), 5.02 (d, J=8.1 Hz, 1H), 4.98 (d, J=7.2 Hz, 1H), 4.81 (m, 2H), 4.76 (d, J=5.7 Hz, 1H), 4.72 (d, J=5.7 Hz, 1H); 3.34 (d, J=7.8 Hz, 1H), 3.97 (dt, J=9.6, 6.0 Hz, 2H), 3.84 (dd, J=9.6, 7.8 Hz, 1H), 3.65-3.40 (m, 3H), 2.41 (dt, J=7.2, 1.5 Hz, 2H), 1.65 9m, 4H), 1.31 (s, 10H), 1.21 (d, J=6.3 Hz, 3H); MS (FAB+): 611.2 ((M+Na)+, 8), 595.2 ((M+Li)+, 100), 567.2 (12), 505.2 (10), 441.1 (7), 401.1 (6).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.[C:9]1(=O)[O:14][C:12](=[O:13])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]12.C(N(CC)CC)C>C1(C)C=CC=CC=1>[N:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:2][N:1]1[C:12](=[O:13])[C:11]2[C:10](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]1=[O:14]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: NCc1ccccn1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2C(=O)N1Cc1ccccn1
Yield: 86.2 %

Procedure:
2-Aminomethylpyridine (4.0 g, 37 mmol) and phthalic anhydride (5.5 g, 37 mmol) were dissolved in toluene (100 ml), and triethylamine (3.7 g, 36 mmol) was added thereto. The mixture was refluxed for 3 hrs. The solvent was evaporated, and the residue was recrystallized from hexane-ethanol to give the titled compound (7.6 g, 86%).
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:19]=[N:20][C:21]([CH3:24])=[CH:22][CH:23]=3)=[CH:14][C:13]2=[O:25])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:27]N(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[OH:58][C@@H:59]([CH2:89]O)[CH2:60][N:61]1[CH:65]=[CH:64][C:63]([NH:66]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:62]1>ClCCl.C(OCC)(=O)C>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:19]=[N:20][C:21]([CH3:24])=[CH:22][CH:23]=3)=[CH:14][C:13]2=[O:25])[C:9]([NH:66][C:63]2[CH:64]=[CH:65][N:61]([CH2:60][C:59]([OH:58])([CH3:89])[CH3:27])[N:62]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(OC2=CC(=O)N([C@@H](CC3CCCCC3)C(=O)O)C2)cn1
Reactant: CCN=C=NCCCN(C)C
Reactant: CC(C)C[C@@H](C(=O)Nc1ccn(C[C@@H](O)CO)n1)N1CC(Oc2cccc(Cl)c2Cl)=CC1=O
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: Cc1ccc(OC2=CC(=O)N([C@@H](CC3CCCCC3)C(=O)Nc3ccn(CC(C)(C)O)n3)C2)cn1
Temperature: 23 °C
Reaction time: 0.25 h
Yield: 54.5 %

Procedure:
To a stirred solution of (S)-3-cyclohexyl-2-[4-(6-methyl-pyridin-3-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (150 mg, 0.4 mmol) in dichloromethane (12 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (249 mg, 1.3 mmol) and N,N-diisopropylethylamine (280 mg, 2.2 mmol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (200 mg, 1.31 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 67 mg, 0.4 mmol) were added to the reaction mixture. The reaction mixture was then stirred at 23° C. for 48 h. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous ammonium chloride solution followed by a saturated aqueous sodium bicarbonate solution. The organic layer was then washed with a saturated aqueous sodium chloride solution, separated, dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (silica gel (100-200 mesh)) which afforded (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(6-methyl-pyridin-3-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionamide (105 mg, 50%) as a light brown sticky solid: NMR (400 MHz, CDCl3) δ ppm 0.89-1.06 (m, 2H), 1.14 (br. s., 6H), 1.17-1.29 (m, 3H), 1.56-1.94 (m, 8H), 2.58 (br. s., 3H), 3.76 (br. s., 1H), 3.92 (br. s., 2H), 4.09 (d, J=18.1 Hz, 1H), 4.33 (d, J=18.1 Hz, 1H), 4.81-4.93 (m, 1H), 4.96 (br. s., 1H), 6.67 (br. s., 1H), 7.20 (d, J=8.8 Hz, 1H), 7.28 (br. s., 1H), 7.41 (d, J=8.3 Hz, 1H), 8.39 (br. s., 1H), 8.74 (br. s., 1H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[CH3:11].C([O-])([O-])=O.[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC(C)=O>[CH2:18]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[CH3:11])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: CC(=O)c1ccc(O)c(C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)c1ccc(OCc2ccccc2)c(C)c1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 99.1 %

Procedure:
A mixture of 4′-hydroxy-3′-methylacetophenone (10.00 g; 66.6 mmol) and K2CO3 (13.80 g; 99.9 mmol) in acetone (100 mL) was stirred, at RT for 40 minutes. Subsequently, benzyl bromide (7.9 mL; 66.6 mmol) was added and the resulting mixture was heated under reflux for 2.5 h. After cooling to RT the mixture was concentrated in vacuo. The residue was dissolved in EtOAc, washed with 5% aqueous ammonia, water, and brine, dried (MgSO4), filtered and concentrated in vacuo to afford 1-(4-benzyloxy-3-methylphenyl)-ethanone (15.86 g).
Reaction SMILES: [CH3:1][N:2](C)[C:3]1C(C)=CC=CC=1.C(OCC)C.[CH2:16]([Li:20])[CH2:17][CH2:18][CH3:19].[CH3:21][CH2:22][CH2:23]CCC>>[CH3:1][N:2]([CH:16]([Li:20])[C:17]1[CH:23]=[CH:22][CH:21]=[CH:19][CH:18]=1)[CH3:3]
Reactant: [Li]CCCC
Reactant: CCCCCC
Reactant: Cc1ccccc1N(C)C
Solvent: CCOCC
Product: [Li]C(c1ccccc1)N(C)C
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 77 %

Procedure:
18 mL (0.12 mmol) of N,N-dimethyl-o-toluidine was placed in a 200 mL glass vessel, to which a mixed solvent of 50 mL of hexane and 16 mL of diethyl ether was added under a nitrogen atmosphere. 50 mL (2.6 mol/L) of a hexane solution of n-butyllithium was slowly added dropwise to the solution under stirring at room temperature over 25 minutes, and the solution was further stirred at room temperature for 45 hours. After completing the reaction, the precipitate was filtered off, and the resulting solid matter was rinsed with hexane and dried under reduced pressure at room temperature to provide 13 g of dimethylaminobenzyllithium (LiCH2C6H4N(CH3)2-o) (yield: 77%).