Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32]CC2C=CC=CC=2)=[C:28]([O:40]CC2C=CC=CC=2)[CH:27]=1)[C:10]([O:12][C@H:13]([CH3:24])[CH2:14][O:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CO>[OH:40][C:28]1[CH:27]=[C:26]([CH2:25][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[C:10]([O:12][C@H:13]([CH3:24])[CH2:14][O:15][C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])=[O:11])[CH:31]=[CH:30][C:29]=1[OH:32]
Reactant: [H][H]
Reactant: C[C@H](COC(=O)c1ccccc1)OC(=O)[C@H](Cc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1)NC(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: C[C@H](COC(=O)c1ccccc1)OC(=O)[C@H](Cc1ccc(O)c(O)c1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.9 %

Procedure:
To a solution of (1R)-1-methyl-2-phenylcarbonyloxyethyl (2S)-2-[(tert-butoxy)carbonylamino]-3-[3,4-bis(phenylmethoxy)phenyl]propanoate (5) (2.6 g, 4.85 mmol) in 40 mL of tetrahydrafuran, 10% Pd—C (200 mg) pre-mixed with 10 mL of methanol was added under a nitrogen atmosphere. The nitrogen atmosphere was exchanged with hydrogen using the evacuation refill cycle method. The mixture was stirred under hydrogen at room temperature for 2 hours. After filtration and washing with methanol, the filtrate was concentrated and chromatographed (silica gel, 30% ethyl acetate in hexane) to afford 1.87 g (100% yield) of the title compound (1). MS (ESI) m/z 460.20 (M+H)+ and 458.17 (M−H)−.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH:8]=[O:9])[C:5]2[C:10]([I:32])=[N:11][N:12]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:4]=2[CH:3]=1.[BH4-].[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[C:5]2[C:10]([I:32])=[N:11][N:12]([C:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:4]=2[CH:3]=1
Reactant: O=Cc1nc(Cl)cc2c1c(I)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: OCc1nc(Cl)cc2c1c(I)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 68.9 %

Procedure:
6-Chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine-4-carbaldehyde (10.26 g, 18.66 mmol) was dissolved in DCM (250 mL) and methanol (125 mL). The reaction mixture was then cooled to 0° C. and sodium borohydride (0.706 g, 18.66 mmol) was added. The reaction mixture was stirred at room temperature for 15 min. The reaction was quenched with water and extracted with DCM. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo while loading on silica gel. Purification by flash chromatography (2-10% DCM/EtOAc) gave (6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol (7.09 g, 12.85 mmol, 69%). MS ESI calc'd. for C26H19ClN3O [M+H]+ 552. found 552.
Reaction SMILES: [CH:1]([NH:3][CH2:4][CH2:5][N:6]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=O.B.C1COCC1>C1COCC1>[CH3:1][NH:3][CH2:4][CH2:5][N:6]1[CH2:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1
Reactant: O=CNCCN1CCCNCC1
Agent: B
Solvent: C1CCOC1
Product: CNCCN1CCCNCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2.75 gm of N-(2-formamidoethyl)homopiperazine in 20 ml of dry THF under N2 is added carefully 60 ml of borane THF solution. After the addition is complete the reaction mixture is heated to reflux for 5 hours then stirred at room temperature overnight. The reaction mixture is quenched by the careful addition of 20 ml of 6N HCl followed by refluxing for 1 hour. The reaction mixture is cooled, 50 ml of water added and solid KOH added carefully to alkaline pH. Extraction with ether gives the desired product N-(2-methylamino)homopiperazine.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)=O)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:22]([NH:24][CH2:25][CH2:26][CH3:27])=[O:23])[C:13]=2[CH2:12][NH:11][C:10]1=[O:35].[CH3:36][N:37]([CH3:42])[CH2:38][CH2:39][CH2:40][NH2:41]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:41][CH2:40][CH2:39][CH2:38][N:37]([CH3:42])[CH3:36])[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:22]([NH:24][CH2:25][CH2:26][CH3:27])=[O:23])[C:13]=2[CH2:12][NH:11][C:10]1=[O:35]
Reactant: CN(C)CCCN
Reactant: CCCNC(=O)c1ccc(C)c(-c2nc(S(C)=O)nc3c2CNC(=O)N3c2c(F)cccc2F)c1
Solvent: ClCCl
Product: CCCNC(=O)c1ccc(C)c(-c2nc(NCCCN(C)C)nc3c2CNC(=O)N3c2c(F)cccc2F)c1
Yield: 77.5 %

Procedure:
To a solution of compound 3-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide (30 mg, 0.06 mmol) in DCM (5 mL) was added N,N-dimethyl-1,3-propanediamine (0.036 mL, 0.30 mmol). The resultant solution was stirred at room temperature over night. The result mixture was concentrated. CombiFlash chromatography (mobile phase DCM/DCM[90]+MeOH[7]+NH4OH[3]) provided the title compound as a white solid (25 mg, 77%). LC-MS m/z 552 (M+H)+; 1H-NMR (MeOD) δ 1.00 (t, 3H), 1.58 (m, 2H), 1.66 (m, 2H), 2.16 (m, 2H), 2.18 (s, 6H), 2.30 (s, 3H), 3.06 (m, 2H), 3.37 (m, 2H), 4.10 (s, 2H), 7.17 (t, 2H), 7.45 (d, 1H), 7.53 (m, 1H), 7.69 (s, 1H), 7.85 (d, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][NH:16][C:17]3[N:22]=[C:21]([C:23](OC)=[O:24])[CH:20]=[CH:19][N:18]=3)[CH2:10][CH2:9]2)[CH:7]=1.[NH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]1[NH:35][CH:36]=[CH:37][C:38](=[O:40])[N:39]=1>C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:27][CH3:28])=[C:6]([N:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][NH:16][C:17]3[N:22]=[C:21]([C:23]([NH:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]4[NH:35][CH:36]=[CH:37][C:38](=[O:40])[N:39]=4)=[O:24])[CH:20]=[CH:19][N:18]=3)[CH2:12][CH2:13]2)[CH:7]=1
Reactant: COC(=O)c1ccnc(NCCN2CCN(c3cc(Cl)ccc3OC)CC2)n1
Reactant: NCCCNc1nc(=O)cc[nH]1
Solvent: CCCCO
Product: COc1ccc(Cl)cc1N1CCN(CCNc2nccc(C(=O)NCCCNc3nc(=O)cc[nH]3)n2)CC1

Procedure:
3.0 g (7.4 mmols) of methyl 2-[[2-[4-(5-chloro-2-methoxyphenyl)piperazin- 1-yl]ethyl]amino]-pyrimidine-4-carboxylate and 1.5 g (8.9 mmols) of 2-[(3-aminopropyl)amino]pyrimidin-4(1H)-one in 20 ml of n-butanol are introduced into a 100 ml, round bottomed flask. The mixture is heated at the reflux temperature of the solvent for 20 hours and then the solvent is evaporated under reduced pressure.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=1.[H-].[Na+].Br[CH2:17][C:18]1[C:19]([Cl:24])=[N:20][CH:21]=[CH:22][CH:23]=1>CN(C=O)C.C(OCC)(=O)C>[Cl:24][C:19]1[C:18]([CH2:17][N:7]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:23][CH:22]=[CH:21][N:20]=1
Reactant: c1cncc(Nc2cccnc2)c1
Reactant: Clc1ncccc1CBr
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Clc1ncccc1CN(c1cccnc1)c1cccnc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 76.8 %

Procedure:
To a solution of N-pyridin-3-ylpyridin-3-amine (510 mg, 3 mmol) in anhydrous DMF (4.5 mL) was added 60% sodium hydride/mineral oil (169 mg, 4.2 mmol). After stirring at ambient temperature for 15 min., 3-(bromomethyl)-2-chloropyridine (677 mg, 3.28 mmol) (preparation described in U.S. Pat. No. 5,739,326) was added neat and the action was stirred for ˜2 hours. The reaction was diluted with ethyl acetate, washed with NaHCO3 solution, then water, and the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. The residue was purified by silica gel chromato-graphy eluting with a 20-90% acetonelhexane gradient to give the purified product which upon trituration with diethyl ether gave the title compound as a tan solid (684 mg, 77% yield). 1H-NMR (500 MHz , CDCl3): δ 8.40 (2H, d, J=2.7 Hz), 8.34 (1H, d, J=4.6 Hz), 8.30 (2H, d, J=4.6 Hz), 7.69 (1H, d, J=7.8 Hz), 7.33-7.35 (2H, br d, J=˜8.3 Hz), 7.20-7.26 (4H, m), 5.04 (2H, s). m/e (m+1): 297.0
Reaction SMILES: [NH2:1][CH2:2][C:3]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1[Cl:18])([OH:10])[CH2:4][N:5]1[CH:9]=[N:8][CH:7]=[N:6]1.[CH2:19]([S:22](Cl)(=[O:24])=[O:23])[CH2:20][CH3:21]>>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[C:3]([OH:10])([CH2:2][NH:1][S:22]([CH2:19][CH2:20][CH3:21])(=[O:24])=[O:23])[CH2:4][N:5]1[CH:9]=[N:8][CH:7]=[N:6]1
Reactant: NCC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl
Reactant: CCCS(=O)(=O)Cl
Product: CCCS(=O)(=O)NCC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl

Procedure:
Following the procedure described in example 1 but using 3-amino-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol and propanesulfonylchloride, the title compound was obtained in a similar yield:
Reaction SMILES: [CH3:1][S-:2].[Na+].[Br:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9](Br)[CH:10]=1>CN(C=O)C.C(OCC)(=O)C>[Br:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([S:2][CH3:1])[CH:10]=1
Reactant: C[S-]
Reactant: Brc1cncc(Br)c1
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CSc1cncc(Br)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88.7 %

Procedure:
Sodium thiomethoxide (1.6 g, 23 mmol) was added to a solution of 3,5-dibromopyridine (5 g, 21 mmol) in DMF (25 mL). After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate and washed several times with brine. The extracts were dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude material was chromatographed on silica (10% ethyl acetate/hexanes) to give the title compound (3.8 g, 89% yield) as a clear oil.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:21])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:14]=2)[O:4]1.BrCCO[Si]([C:29](C)([CH3:31])[CH3:30])(C)C.CCN(C(C)C)C(C)C.[I-].[K+]>CN(C=O)C>[CH3:30][CH:29]([N:18]1[CH2:19][CH2:20][CH:15]([N:13]2[CH:14]=[C:10]([B:5]3[O:6][C:7]([CH3:8])([CH3:9])[C:3]([CH3:21])([CH3:2])[O:4]3)[CH:11]=[N:12]2)[CH2:16][CH2:17]1)[CH3:31]
Reactant: CC1(C)OB(c2cnn(C3CCNCC3)c2)OC1(C)C
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)N1CCC(n2cc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Temperature: 50 °C

Procedure:
A solution of 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine hydrochloride (500 mg, 1.59 mmol) in DMF (15.0 mL) was charged with (2-bromoethoxy)-tert-butyldimethylsilane (0.376 mL, 1.75 mmol), DIPEA (0.694 mL, 3.99 mmol) and potassium iodide (26 mg, 0.16 mmol) and was heated at 50° C. for 16 h. The DMF was then concentrated in vacuo. The product was purified by flash chromatography (0 to 15% MeOH:EtOAc) to afford the title compound. 1H NMR (400 MHz, CD3OD): δ 7.90 (s, 1H), 7.69 (s, 1H), 4.31 (td, J=7.71, 15.41 Hz, 1H), 3.88 (t, J=5.68 Hz, 2H), 3.28 (br s, 2H), 3.00 (s, 3H), 2.86 (s, 3H), 2.76-2.84 (m, 2H), 2.51-2.67 (m, 2H), 2.10-2.19 (m, 4H), 1.31 (s, 12H), 0.91-0.94 (m, 9H); MS (ESI): 436.28 [M+H]+; HPLC tR=1.26 min (TOF polar—3 min).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1)=[O:3].O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.[CH:37]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[S:46][CH:47]([C:51](O)=[O:52])[C:48](O)=[O:49])([CH3:39])[CH3:38]>C(Cl)Cl>[CH2:11]([O:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]2[O:3][C:48](=[O:49])[C:47]([S:46][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[CH:37]([CH3:38])[CH3:39])=[C:51]([OH:52])[CH:1]=2)=[CH:5][CH:6]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(=O)c1ccc(OCc2ccccc2)cc1
Reactant: CC(C)c1ccccc1SC(C(=O)O)C(=O)O
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)c1ccccc1Sc1c(O)cc(-c2ccc(OCc3ccccc3)cc2)oc1=O

Procedure:
The title compound was prepared by Method A using 4-benzyloxyacetophenone (0.3 g, 0.675 mmol), trimethylsilyl triflate (0.15 g, 0.675 mmol), triethylamine (0.14 g, 1.35 mmol), methylene chloride (20 mL), and diethyl ester of [(2-isopropylphenyl)thio]propanedioic acid (0.210 g, 0.675 mmol). m.p. 163-165° C.; 1H NMR (400 MHz, DMSO-d6) δ1.28 (d, 6H), 3.4 (m, 1H), 5.22 (s, 2H), 6.64(s,1H), 6.92 (d, 1H), 7.06 (t, 1H), 7.11(t, 1H), 7.19 (d, 1H), 7.28 (d, 1H), 7.36 (q, 2H), 7.42 (d, 2H), 7.49 (d, 2H), 7.83 (d, 2H).
Reaction SMILES: [NH2:1][C:2]([CH3:6])=[CH:3][C:4]#[N:5].CC1(C)[O:13][C:12](=O)[CH:11]=[C:10]([CH3:15])O1>CCOC(C)=O>[CH3:6][C:2]1[NH:1][C:10]([CH3:15])=[CH:11][C:12](=[O:13])[C:3]=1[C:4]#[N:5]
Reactant: CC1=CC(=O)OC(C)(C)O1
Reactant: CC(N)=CC#N
Solvent: CCOC(C)=O
Product: Cc1cc(=O)c(C#N)c(C)[nH]1
Temperature: 130 °C
Yield: 19.4 %

Procedure:
A 250 mL round bottom flask was charged with 3-aminobut-2-enenitrile (10.00 g, 122 mmol), 2,2,6-trimethyl-4H-1,3-dioxin-4-one (32.4 mL, 244 mmol), and a magnetic stir bar. The flask was equipped with a reflux condenser and a CaCl2 tube and the reaction mixture was heated at 130° C. for 1 h. The reaction was allowed to cool room temperature and was diluted with EtOAc (100 mL). The solid that formed was collected, washed with EtOAc (20 mL), and dried to give 2,6-dimethyl-4-oxo-1,4-dihydropyridine-3-carbonitrile (3.5 g, 23.62 mmol, 19.4% yield) as a beige soild. 1H NMR (400 MHz, DMSO-d6) δ 11.94 (br. s., 1H), 6.04 (s, 1H), 2.41 (s, 3H), 2.21 (s, 3H). MS(ES) [M+H]+ 148.9.
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH2:5])[CH3:2].[C:10]([CH:14]1CC2O[CH:15]1C=C2)(OC)=[O:11].Cl.C(Cl)Cl>O>[CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH:5][C:10](=[O:11])[CH:14]=[CH2:15])[CH3:2]
Reactant: CCCCC(CC)CN
Reactant: COC(=O)C1CC2C=CC1O2
Agent: Cl
Solvent: O
Solvent: ClCCl
Product: C=CC(=O)NCC(CC)CCCC
Temperature: 140 °C
Reaction time: 15 h

Procedure:
7.2 parts 30% methanolic Na-methylate solution are added to 64.5 parts 2-ethylhexylamine. 77 parts 2-carbomethoxy-7-oxabicyclo(2,2,1)hept-5-ene are added drop-wise at 30° to 35° C. during cooling. The reaction medium is then stirred for 15 hours and neutralised with 4 parts concentrated hydrochloric acid. 100 parts methylene chloride and 50 parts water are added, the organic phase separated off, and the aqueous phase extracted twice with 25 ml methylene chloride in each instance. The combined organic phases are reduced in a rotary evaporator at a bath temperature of 90° C. and a vacuum of 20 Torr. The residue is heated under a high vacuum to 110° to 120° C. (bath temperature 140° C.). On conclusion of the furane separation, the sedimentation temperature increases and the product distills over. 66.6 parts N(2-ethylhexyl)acrylamide with a boiling point of 123° C. at 0.4 Torr are obtained.
Reaction SMILES: [F:1][C:2]1([C:16]([F:19])([F:18])[F:17])[O:7][C:6]([F:9])([F:8])[C:5](F)([C:10]([F:13])([F:12])[F:11])[O:4][C:3]1=[O:15].[O-2].[Ca+2].[O:22]=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>O>[O:15]=[C:3]1[C:2]([F:1])([C:16]([F:17])([F:18])[F:19])[O:7][C:6]([F:9])([F:8])[C:5]([OH:22])([C:10]([F:12])([F:11])[F:13])[O:4]1
Reactant: O=C1OC(F)(C(F)(F)F)C(F)(F)OC1(F)C(F)(F)F
Reactant: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Agent: [Ca+2]
Agent: [O-2]
Solvent: O
Product: O=C1OC(O)(C(F)(F)F)C(F)(F)OC1(F)C(F)(F)F

Procedure:
Perfluoro(2-oxo-3,6-dimethyl-1,4-dioxane), 314 g (1.01 mol), was added dropwise to a slurry of 56.1 g (1.0 mol) of calcium oxide in 500 ml of water while the slurry was stirred in an ice bath. The resultant mixture was stirred for one hour, heated nearly to reflux for 30 min, and stirred for about 65 h. Upon evaporation of the water, the crystalline residue which remained was treated portionwise with 450 g (3.2 mol) of P2O5. The resultant mixture was heated slowly (exothermic reaction) to 150° and then distilled to give 246 g of crude 2-oxo-6-hydroxyperfluoro(3,6-dimethyl-1,4-dioxane), bp 70°-75° (50 mm); upon redistillation from a small amount of P2O5 208 g (67%) of purified lactol was recovered, bp 71°-73° (50 mm). IR: 2.90 (free OH), 5.51 (fluorolactone C=O), 7.5-10μ (C--F, C--O). NMR: 19F -82.7 (several m, 7, CF3 +part of AB for O--CF2) -113.0 and 115.6 ppm (m, 1 CF).
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:12]=[C:13]([NH2:16])[S:14][CH:15]=2)[CH:8]=[CH:9][CH:10]=1)([O-:4])=[O:3].[O:17]1[C:21]2[CH:22]=[CH:23][C:24]([S:26](Cl)(=[O:28])=[O:27])=[CH:25][C:20]=2[O:19][CH2:18]1.Cl>N1C=CC=CC=1>[N+:2]([C:5]1[CH:6]=[C:7]([C:11]2[N:12]=[C:13]([NH:16][S:26]([C:24]3[CH:23]=[CH:22][C:21]4[O:17][CH2:18][O:19][C:20]=4[CH:25]=3)(=[O:27])=[O:28])[S:14][CH:15]=2)[CH:8]=[CH:9][CH:10]=1)([O-:4])=[O:3]
Reactant: Nc1nc(-c2cccc([N+](=O)[O-])c2)cs1
Reactant: O=S(=O)(Cl)c1ccc2c(c1)OCO2
Agent: Cl
Solvent: c1ccncc1
Product: O=[N+]([O-])c1cccc(-c2csc(NS(=O)(=O)c3ccc4c(c3)OCO4)n2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 38.1 %

Procedure:
A mixture of 0.5 g 4-(3-nitro-phenyl)-thiazol-2-ylamine hydrochloride with 0.52 g of benzo[1,3]dioxol-5-sulfonyl chloride was stirred overnight with 2 ml of pyridine. The resulting, red colored suspension was poured into 25 ml of 1N hydrochloric acid and the solid which thereby separated was filtered off and dissolved in a mixture of 30 ml of ethanol and 20 ml of 2N sodium hydroxide solution. After the addition of 0.5 g of active charcoal the mixture was stirred at room temperature for 30 minutes and subsequently the active charcoal was filtered off. The product separated upon neutralization with concentrated hydrochloric acid. Recrystallization from 100 ml of 60% ethanol yielded 0.30 g of benzo[1,3]dioxol-5-sulfonic acid [4-(3-nitro-phenyl)-thiazol-2-yl]-amide as yellowish crystals.
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([O:13][CH3:14])=[C:7]([O:15][CH3:16])[C:6]=1[O:17][CH3:18].C([Li])CCC.CN([CH:27]=[O:28])C.O>CCOCC>[CH3:1][O:2][CH2:3][O:4][C:5]1[C:6]([O:17][CH3:18])=[C:7]([O:15][CH3:16])[C:8]([O:13][CH3:14])=[C:9]([O:11][CH3:12])[C:10]=1[CH:27]=[O:28]
Reactant: CN(C)C=O
Reactant: COCOc1cc(OC)c(OC)c(OC)c1OC
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: COCOc1c(C=O)c(OC)c(OC)c(OC)c1OC
Temperature: -20 °C

Procedure:
6.2 g of 1-methoxymethyloxy-2,3,4,5-tetramethoxybenzene prepared in Referential Example 13 was dissolved in 50 ml of anhydrous ether, and 18 ml of n-butyllithium (1.6M n-hexane solution) was dropwise added thereto at -20° C. while stirring. After the mixture was stirred at 0° C. for 30 min, the temperature was returned to -20° C. and 3.5 ml of DMF was dropwise added thereto. After 100 ml of water was added thereto, the mixture was extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=7:3) to prepare 5.6 g of the product compound as a light yellow oleaginous substance.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[N:10]=[C:9]([C:11]([Cl:14])([Cl:13])[Cl:12])[N:8]=[C:7](C(Cl)(Cl)Cl)[N:6]=1.[NH3:19].O>O1CCCC1>[NH2:19][C:7]1[N:6]=[C:5]([CH2:4][CH2:3][CH2:2][Cl:1])[N:10]=[C:9]([C:11]([Cl:12])([Cl:13])[Cl:14])[N:8]=1
Reactant: N
Reactant: ClCCCc1nc(C(Cl)(Cl)Cl)nc(C(Cl)(Cl)Cl)n1
Solvent: C1CCOC1
Solvent: O
Product: Nc1nc(CCCCl)nc(C(Cl)(Cl)Cl)n1
Reaction time: 0.5 h

Procedure:
102.3 g of 2-(3-chloro-n-propyl)-4,6-bis-(trichloromethyl)-1,3,5-triazine are dissolved in 100 ml of tetrahydrofuran, and to this solution are added at room temperature, with stirring, 400 ml of concentrated aqueous ammonia solution. After 30 minutes, 500 ml of water are addded, and the reaction mixture is extracted twice with 100 ml of ether each time. The ether phases are dried over magnesium sulfate, filtered, and concentrated by evaporation to leave 68.3 g of title product in the form of light-brown oil.
Reaction SMILES: [C:1]([NH:11][C@H:12]([C:16]([O:18][CH2:19][CH:20]([O:30][C:31](=[O:49])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH2:21][C:22]([CH3:29])([CH3:28])[C:23]([O:25][CH2:26]Cl)=[O:24])=[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].[I-:50].[Na+]>C(#N)C>[C:1]([NH:11][C@H:12]([C:16]([O:18][CH2:19][CH:20]([O:30][C:31](=[O:49])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH2:21][C:22]([CH3:29])([CH3:28])[C:23]([O:25][CH2:26][I:50])=[O:24])=[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]
Reactant: [I-]
Reactant: CCCCCCCCCCCCCCCCCC(=O)OC(COC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)CC(C)(C)C(=O)OCCl
Agent: [Na+]
Solvent: CC#N
Product: CCCCCCCCCCCCCCCCCC(=O)OC(COC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)CC(C)(C)C(=O)OCI
Temperature: 60 °C
Reaction time: 4 h
Yield: 88.9 %

Procedure:
To a solution of chloromethyl 5-(N-CBz-L-valyloxy)-4-stearoyloxy-2,2-dimethylvalerate (7.8 g, 11 mmol) in acetonitrile (100 mL), was added sodium iodide (6.5 g, 44 mmol). The solution was stirred for 4 h at 60° C. The resulting suspension was filtered and the filtrate was evaporated. The residue was dissolved in CH2Cl2 and washed with aqueous sodium thiosulfate (0.1 M). The organic phase was dried (Na4SO4) and concentrated under reduced pressure. The crude product was column chromatographed (silica gel, 1% MeOH in CH2Cl2), to give 7.84 g of iodomethyl 5-(N-CBz-L-valyloxy)-4-stearoyloxy-2,2-dimethylvalerate
Reaction SMILES: [CH2:1]([C:4]1[S:5][C:6]([CH3:9])=[CH:7][CH:8]=1)[CH:2]=[CH2:3].[Cl:10][SiH:11]([Cl:13])[Cl:12]>[Pt].C1(C)C=CC=CC=1>[Cl:10][Si:11]([Cl:13])([Cl:12])[CH2:3][CH2:2][CH2:1][C:4]1[S:5][C:6]([CH3:9])=[CH:7][CH:8]=1
Reactant: Cl[SiH](Cl)Cl
Reactant: C=CCc1ccc(C)s1
Agent: [Pt]
Solvent: Cc1ccccc1
Product: Cc1ccc(CCC[Si](Cl)(Cl)Cl)s1

Procedure:
The hydrosilylation reaction of Example 1 was repeated using 4.5 g of 2-allyl-5-methylthiophene in place of 2-allylthiophene, 2.5 g of anhydrous toluene, 5.0 g of trichlorosilane, and 50 mg of Platinum Catalyst. 2-(3-Trichlorosilylpropyl)-5-methylthiophene was obtained as a colorless liquid: 1H NMR (CDCl3) δ 6.60 (m, 2H); 2.88 (t, 2H, J=7.2 Hz); 2.47 (s, 3H); 1.95 (m, 2H); 1.47 (m, 2H).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH2:9])[C:3]=1[O:10][CH2:11][CH:12]([O:14]C1CCCCO1)[CH3:13].C(O[CH:24]=[C:25]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])C>>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH:9][CH:24]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:3]=1[O:10][CH2:11][CH:12]([OH:14])[CH3:13]
Reactant: CC(COc1c(N)ccc(F)c1F)OC1CCCCO1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Product: CCOC(=O)C(=CNc1ccc(F)c(F)c1OCC(C)O)C(=O)OCC
Reaction time: 1.5 h

Procedure:
To the total amount of the product obtained in Example 2 was added 1.24 g of diethyl ethoxymethylenemalonate (XVI, Y=EtO, alkyl=Et, hereinafter abbreviated as EMME). The mixture was heated to 145° to 150° C. with stirring. After 1.5 hours, the system was evacuated to remove formed ethanol, and the mixture was heated a further 30 minutes with stirring under reduced pressure. After cooling, the product was isolated through silica gel column chromatography to yield 1.33 g of the titled compound, which has no tetrahydropyranyl moiety.