Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9])#N.Cl.C([N:13]([CH2:16]C)CC)C.[N-:18]=[N+:19]=[N-:20].[Na+]>C1(C)C=CC=CC=1>[N:13]1[CH:16]=[N:20][N:19]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[N:18]=1
Reactant: CCN(CC)CC
Reactant: N#Cc1ccccc1O
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Oc1ccccc1-n1ncnn1
Yield: 97.1 %

Procedure:
A slurry of 2-cyano phenol (25 g, 209.87 mmol), triethylamine hydrochloride (43.3 g, 314.81 mmol), and sodium azide (20.5 g, 314.81 mmol) in toluene (200 mL) is heated to the reflux temperature of the mixture and then the mixture is allowed to stir at reflux for 15 hours. The mixture is cooled and washed with water (200 mL). The aqueous layer is washed with ether (100 mL), made acidic with concentrated HCl, and the resulting solid is collected by filtration. The solid is washed twice with water (200 mL) and dried under vacuum at 100° C. for 15 hours to give 33.05 g of 2-(tetrazol-3-yl)phenol (97%).
Reaction SMILES: CC(O[C:5]([CH3:7])=[O:6])=O.[CH3:8][C@H:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C@H:10]1[NH2:18].[OH-].[K+]>C1(C)C=CC=CC=1.O>[CH3:8][C@H:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C@H:10]1[NH:18][C:5](=[O:6])[CH3:7]
Reactant: CC(=O)OC(C)=O
Reactant: C[C@H]1Cc2ccccc2[C@H]1N
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(=O)N[C@@H]1c2ccccc2C[C@@H]1C
Temperature: 90 °C
Reaction time: 2 h

Procedure:
To a solution of Ac2O (1.45 g, 14.2 mmole) in toluene (12 ml), was added dropwise a solution of (rac), (cis)-2-methyl-1-aminoindan (Ex. 39, 1.85 g, 12.6 mmole). The mixture was heated at 90° C. for 15 min, cooled to 70° C., and a solution of 1.1 g KOH in 8.3 ml water was added. The reaction mixture was stirred at ambient temperature for 2 hrs; the solid was collected by filtration, washed with toluene (10 ml), dried and crystallized from hexane:EtOAc, to give 1.85 g (9.8 mmole, 78%), mp: 146°-7° C.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].CN(C=O)C.[NH2:11][C:12]1[S:13][C:14]2[C:19](O)=[N:18][C:17]([S:21][C@H:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[CH3:23])=[N:16][C:15]=2[N:31]=1.O>O1CCOCC1>[Cl:3][C:19]1[C:14]2[S:13][C:12]([NH2:11])=[N:31][C:15]=2[N:16]=[C:17]([S:21][C@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[F:30])[CH3:23])[N:18]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: C[C@H](Sc1nc(O)c2sc(N)nc2n1)c1ccccc1F
Solvent: C1COCCO1
Solvent: CN(C)C=O
Solvent: O
Product: C[C@H](Sc1nc(Cl)c2sc(N)nc2n1)c1ccccc1F
Temperature: 80 °C
Reaction time: 2 h
Yield: 87.6 %

Procedure:
POCl3 (2.77 mL, 29.7 mmol) was added to DMF (3.07 mL, 39.6 mmol) in dioxane (30 mL). After 30 minutes this mixture was added to a solution of 2-amino-5-{[(1S)-1-(2-fluorophenyl)ethyl]thio}[1,3]thiazolo[4,5-d]pyrimidin-7-ol (6.38 g, 19.8 mmol) in dioxane (100 mL). After 30 minutes POCl3 (2.77 mL, 29.7 mmol) was added, the reaction mixture was heated to 80° C. for 2 h. After cooling to room temperature, water (20 mL) was carefully added and the resulting mixture was stirred at 80° C. for 30 minutes and at room temperature for 2 h. The reaction mixture was poured into water and the formed precipitate was collected. The solid was purified by flash column chromatography (5% MeOH in CHCl3) to give the title compound (5.91 g, 88% yield).
Reaction SMILES: C(OCC=C)C=C.[C:8]1([OH:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:15]1([OH:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23]1>C(OCCOCCO)C>[C:8]1([OH:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:15]1([OH:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:24]([C:25]1([CH2:26][CH:27]=[CH2:28])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:29][CH2:30]1)[CH:23]=[CH2:22]
Reactant: c1ccc2c(c1)CCC2
Agent: C=CCOCC=C
Solvent: CCOCCOCCO
Solvent: Oc1ccccc1
Product: C=CCC1(CC=C)CCc2ccccc21
Yield: 75 %

Procedure:
140 grams of the diallyl ether of indane bisphenol was placed into a one liter round bottom flask containing a magnetic stir bar and dissolved in 210 grams of 2-(2-ethoxyethoxy) ethanol. The solution was deoxygenated by bubbling dry argon gas through the solution for 15 minutes, and then a reflux condenser was attached. The solution was refluxed for 6 hours under an inert atmosphere. The solvent was removed by vacuum distillation between 60° and 62° C., and the product was collected between 210° and 214° C. as a light yellow, viscous liquid (13.3 Pa). Diallyl indane bisphenol was so viscous that the condenser on the still has to be heated with a hot air gun so that the product could flow into the collection flask; 110 grams of diallyl indane bisphenol were isolated (75% yield overall).
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].N1C=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].Cl.[O:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>>[C:20]([NH:4][C:3]1[C:2](=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:1]([OH:10])=[O:9])(=[O:19])[CH2:21][CH2:22][CH2:23][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: Nc1ccccc1C(=O)O
Reactant: C1CCOC1
Reactant: c1ccncc1
Agent: Cl
Agent: [Cl-]
Product: CCCCCCCC(=O)Nc1ccccc1C(=O)O
Yield: 79.4 %

Procedure:
Anthranilic acid was dissolved in a mixed solvent containing pyridine and tetrahydrofuran (THF) in 5:5 ratio and a THF solution of n-caprioyl chloride was dropped to the solution during several hours for reaction. After the reaction, hydrochloric acid was added to the reaction mixture. Pyridine hydrochloride was filtered and the solvent was removed. N-n-octanoylanthranilic acid was obtained from the remaining reactant after the purification by column chromatography with the yield of 79.4%.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[C:5]#[CH:6])[CH3:2].[NH2:8][N:9]([CH3:12])C=O.[O:13]1CCOC[CH2:14]1>>[CH2:1]([O:3][C:4](=[O:7])[CH2:5][CH:6]=[N:8][NH:9][CH2:12][CH:14]=[O:13])[CH3:2]
Reactant: C#CC(=O)OCC
Reactant: C1COCCO1
Reactant: CN(N)C=O
Product: CCOC(=O)CC=NNCC=O
Yield: 93 %

Procedure:
39.24 g (0.4 mol) of propiolic acid ethyl ester were added to a solution of 29.63 g (0.4 mol) of N-amino-N-methylformamide in 80 ml of dioxane and left standing for 3 weeks at room temperature. The yellow solution was evaporated at 40° C./30 torr and the residue filtered over a silical gel column (350 g) with a mixture of dichloromethane/n-hexane 49:1 in fractions of 250 ml each. Fractions 2 to 10 were united and evaporated at 40° C./30 torr, yielding 63.9 g (93%) of 3-(formylmethylhydrazono)-propionic acid ethyl ester as a yellow fluid (IR: 3462, 2984, 1735, 1688, 1629, 1183, 1045 cm-1).
Reaction SMILES: [CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][O:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[C:12]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([OH:25])[CH:23]=4)[NH:18][N:17]=3)[NH:13]2)=[CH:9][CH:8]=1)[CH3:2].[N+](C1C=C[C:34]([O:37][P:38]([CH3:50])(=O)[O:39]C2C=CC([N+]([O-])=O)=CC=2)=CC=1)([O-])=O.N12CCCN=C1CCCCC2.CO>ClCCl>[CH3:34][O:37][P:38]([CH3:50])(=[O:39])[O:25][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[C:16]2[C:12]1[NH:13][C:14]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:6][CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:26][CH3:27])[CH:15]=2
Reactant: CP(=O)(Oc1ccc([N+](=O)[O-])cc1)Oc1ccc([N+](=O)[O-])cc1
Reactant: CCN(CC)CCOc1ccc2cc(-c3n[nH]c4ccc(O)cc34)[nH]c2c1
Solvent: CO
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CCN(CC)CCOc1ccc2cc(-c3n[nH]c4ccc(OP(C)(=O)OC)cc34)[nH]c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 24 %

Procedure:
The compound methylphosphonic acid 3-[6-(2-diethylamino-ethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester methyl ester is prepared as follows: 100 mg of 3-[6-(2-diethylaminoethoxy)-1H-indol-2-yl]-1H-indazol-5-ol in solution in 4 ml of dichloromethane with 93 mg of methylphosphonic acid bis-(4-nitrophenyl)ester (prepared according to procedure E) are stirred at ambient temperature. A solution of 41 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in 1 ml of dichloromethane is added dropwise. The solution is stirred overnight at ambient temperature. 41 μl of DBU, followed by 115 μl of methanol, are then added. This operation is repeated after stirring for 4 h 15 min. After stirring for another hour at ambient temperature, the solvent is evaporated off and the crude is purified by flash chromatography on a cartridge of 25 g of silica, eluent: dichloromethane/methanol, 90/10 to 60/40 in steps. The fractions obtained are concentrated and purified by preparative LC/MS to isolate 30 mg of methylphosphonic acid 3-[6-(2-diethylaminoethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester methyl ester in the form of a colorless oil.
Reaction SMILES: C1(C)C=CC(S([O-])(=O)=O)=CC=1.[CH2:12]([N:19]1[C:23](=[O:24])[C:22](=[C:25]2[N:29]([CH3:30])[C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[S:26]2)[S:21][CH2+:20]1SC)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CC#N>[CH2:12]([N:19]1[C:23](=[O:24])[C:22](=[C:25]2[N:29]([CH3:30])[C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[S:26]2)[S:21][C:20]1=[N:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccccc1
Reactant: CS[CH2+]1SC(=C2Sc3ccccc3N2C)C(=O)N1Cc1ccccc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CC#N
Product: CN1C(=C2SC(=Nc3ccccc3)N(Cc3ccccc3)C2=O)Sc2ccccc21
Temperature: 50 °C
Yield: 28.8 %

Procedure:
To an 8 mL vial was added 3-benzyl-5-(3-methyl-3H-benzothiazol-2-ylidene)-2-methylthio-4-oxo-2-thiazolium p-toluenesulfonate (100 mg, 0.18 mmol), aniline (16 μL, 0.18 mmol) and anhydrous MeCN (1 mL). After warming the mixture to 50° C., TEA (0.10 mL, 0.56 mmol) was added and continued heating the mixture at 50° C. for 12 h. After cooling to room temperature, the resulting precipitates were filtered under reduced pressure, washed with MeCN (2 mL) and dried under vacuum to yield the title product (22.3 mg, 29%) as a yellow solid. 1H-NMR (CDCl3): δ 7.59 (2H, m), 7.48 (1H, dd), 7.26-7.39 (6H, m), 7.10-7.18 (2H, m) 7.01 (3H, m), 5.16 (2H, s), 3.71 (3H, s); MS(ESI): 430 (MH+).
Reaction SMILES: [CH2:1]1[N:11]2[C:12]3[C:8]([CH:9]4[CH2:17][CH2:16][NH:15][CH2:14][CH2:13][CH:10]42)=[CH:7][CH:6]=[CH:5][C:4]=3[O:3][CH2:2]1.Cl[CH2:19][CH2:20][CH2:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)=[O:23].CCN(C(C)C)C(C)C>O1CCOCC1>[CH2:1]1[N:11]2[C:12]3[C:8]([CH:9]4[CH2:17][CH2:16][N:15]([CH2:19][CH2:20][CH2:21][C:22]([C:24]5[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=5)=[O:23])[CH2:14][CH2:13][CH:10]42)=[CH:7][CH:6]=[CH:5][C:4]=3[O:3][CH2:2]1
Reactant: O=C(CCCCl)c1ccc(F)cc1
Reactant: c1cc2c3c(c1)C1CCNCCC1N3CCO2
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: O=C(CCCN1CCC2c3cccc4c3N(CCO4)C2CC1)c1ccc(F)cc1
Temperature: 25 °C

Procedure:
1,2,7,8,9,10,11,11a-octahydro-6bH-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole (97.8 mg, 0.42 mmol), 4-chloro-1-(4-fluorophenyl)-1-butanone (172 mg, 0.86 mmol), KI (71.2 mg, 0.43 mmol), and DIEA (550 mg, 4.3 mmol) were suspended in dioxane (2 mL). The reaction mixture was refluxed for 18 hrs. After cooling to rt, the solution was concentrated. The residue was immediately purified by column chromatography to afford the title compound. MS-ESI: 395[MH]+.
Reaction SMILES: [Cl-].Cl[C:3](Cl)=[N+:4]([CH3:6])[CH3:5].[CH2:8]([N:13]1[C:21]2[N:20]=[CH:19][NH:18][C:17]=2[C:16](=[O:22])[NH:15]/[C:14]/1=[N:23]/[NH2:24])[CH2:9][CH2:10][CH2:11][CH3:12]>C(Cl)Cl>[CH3:5][N:4]([CH3:6])[C:3]1[N:15]2[C:16](=[O:22])[C:17]3[NH:18][CH:19]=[N:20][C:21]=3[N:13]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[C:14]2=[N:23][N:24]=1
Reactant: CCCCCn1/c(=N\N)[nH]c(=O)c2[nH]cnc21
Reactant: C[N+](C)=C(Cl)Cl
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCCn1c2nc[nH]c2c(=O)n2c(N(C)C)nnc12
Reaction time: 0.08 h
Yield: 69.1 %

Procedure:
To methylene chloride (10 mL) was added [B] N-(dichloromethylene)-N-methylmethanaminium chloride (0.21 g, 1.3 mmol) After stirring for 5 mins, (2Z)-3-pentyl-3,7-dihydro-1H-purine-2,6-dione 2-hydrazone (0.10 g, 0.42 mmol) was added, and the mixture was stirred at rt for 5 hrs. LCMS analysis showed product as a major peak was formed. 1N NaoH was carefully added to neutralize the acid, and the mixture was extracted with methylene chloride three times. The combined organic layers were dried by MgSO4, filtered and concentrated in vacuo to yield the desired product (84 mg, 69%). LCMS calculated for C13H20N7O (M+H): 290.2. Found 290.1.
Reaction SMILES: [NH2:1][CH:2]([C:8]#[N:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH:10]([O-])([O-])OCC.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1>C(#N)C>[NH2:9][C:8]1[N:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]=[N:1][C:2]=1[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)C(N)C#N
Reactant: Nc1ccccn1
Reactant: CCOC([O-])[O-]
Solvent: CC#N
Product: CCOC(=O)c1ncn(-c2ccccn2)c1N
Yield: 71.9 %

Procedure:
In 230 ml of acetonitrile, 8.5 g of ethyl α-aminocyanoacetate, 10.8 g of ethyl orthoformate and 6.2 g of 2-aminopyridine were heated under reflux for 1.5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and crystals precipitated were filtered off and washed with benzene to give 11.0 g of the desired compound. m.p.: 129° to 131° C.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:11]2([CH2:13][CH2:12]2)[O:10][C:9](=[O:14])[C:8]=1[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)=[CH:17][CH:16]=1)(=O)=O.[N:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[N:35]1[CH:40]=[CH:39][C:38]([C:7]2[C:11]3([CH2:12][CH2:13]3)[O:10][C:9](=[O:14])[C:8]=2[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]=3)=[CH:17][CH:16]=2)=[CH:37][CH:36]=1
Reactant: OB(O)c1ccncc1
Reactant: O=C1OC2(CC2)C(OS(=O)(=O)C(F)(F)F)=C1c1ccc(OCc2ccc3ccccc3n2)cc1
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: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: O=C1OC2(CC2)C(c2ccncc2)=C1c1ccc(OCc2ccc3ccccc3n2)cc1
Reaction time: 0.5 h
Yield: 17.8 %

Procedure:
To a room temperature, stirred solution of 5-oxo-6-(4-(quinolin-2-ylmethoxy)phenyl)-4-oxaspiro[2,4]hept-6-en-7-yl trifluoromethanesulfonate (200 mg, 0.4 mmol) in 1,4-dioxane (10 mL) were added pyridin-4-ylboronic acid (74 mg, 0.6 mmol), Na2CO3 (102 mg, 1.2 mmol) and water (4 mL) under an inert atmosphere. The mixture was stirred for 30 minutes and then Pd(PPh3)4 (46 mg, 0.04 mmol) was added and the mixture refluxed for 16 h. The reaction mixture was then diluted with water and extracted with EtOAc (2×40 mL). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated in vacuo to afford 7-(pyridin-4-yl)-6-(4-(quinolin-2-ylmethoxy)phenyl)-4-oxaspiro[2.4]hept-6-en-5-one (30 mg, 18%) as a white solid. 1H NMR (500 MHz, d6-DMSO): δ 8.64-8.61 (m, 2 H), 8.40 (d, J=7.2 Hz, 1 H), 8.02-7.99 (m, 2 H), 7.81-7.77 (m, 1 H), 7.67-7.51 (m, 3 H), 7.38-7.24 (m, 5 H), 5.36 (s, 2 H), 1.88-1.85 (m, 2 H), 1.24-1.21 (m, 2 H), MS: M+H: m/z=421.2; M+Na: m/z=443.2. HPLC: 92%, (Condition-I).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]([Cl:7])=[O:6].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])=[N:16][CH:15]=[C:14]([Br:25])[CH:13]=2.C(Cl)(Cl)Cl>C(#N)C>[ClH:7].[Br:25][C:14]1[CH:13]=[C:12]2[C:17]([C:18]([NH:19][CH2:20][C:21]([OH:23])([CH3:22])[CH3:24])=[C:9]([NH:8][C:5](=[O:6])[CH2:4][CH2:3][O:2][CH3:1])[CH:10]=[N:11]2)=[N:16][CH:15]=1
Reactant: COCCC(=O)Cl
Reactant: CC(C)(O)CNc1c(N)cnc2cc(Br)cnc12
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: COCCC(=O)Nc1cnc2cc(Br)cnc2c1NCC(C)(C)O
Product: Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 82 %

Procedure:
3-Methoxypropionyl chloride (24.90 g, 203 mmol) was added over a period of 5 minutes to a mixture of 1-[(3-amino-7-bromo[1,5]naphthyridin-4-yl)amino]-2-methylpropan-2-ol (52.70 g, 169 mmol), chloroform (100 mL), and acetonitrile (530 mL). The reaction mixture was stirred at ambient temperature overnight. The precipitated solid was isolated by filtration, washed well with acetonitrile, and then dried to provide 60.10 g of N-{7-bromo-4-[(2-hydroxy-2-methylpropyl)amino][1,5]naphthyridin-3-yl}-3-methoxypropionamide hydrochloride as a brown solid, mp 206-208° C.
Reaction SMILES: C(N(CC)C(C)C)(C)C.[C:10]1([N:16]=[C:17]=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Si:19]([O:26][C:27]1[CH:32]=[C:31]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH:30]=[CH:29][C:28]=1[C@H:41]1[CH2:46][CH2:45][C@H:44]([OH:47])[CH2:43][CH2:42]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>ClCCl>[C:10]1([NH:16][C:17](=[O:18])[O:47][C@H:44]2[CH2:43][CH2:42][C@H:41]([C:28]3[CH:29]=[CH:30][C:31]([O:33][Si:34]([C:37]([CH3:38])([CH3:39])[CH3:40])([CH3:36])[CH3:35])=[CH:32][C:27]=3[O:26][Si:19]([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:21])[CH3:20])[CH2:46][CH2:45]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc([C@H]2CC[C@H](O)CC2)c(O[Si](C)(C)C(C)(C)C)c1
Reactant: O=C=Nc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1ccc([C@H]2CC[C@H](OC(=O)Nc3ccccc3)CC2)c(O[Si](C)(C)C(C)(C)C)c1
Reaction time: 96 h

Procedure:
N,N-Diisopropylethylamine (100 μl) and phenylisocyanate (55 μl) were added to a stirred solution of trans-4-(2,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)cyclohexanol (50 mg) in anhydrous dichloromethane (2 ml). After 96 hr at 40° C., the reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml). The aqueous layer was extracted with ethyl acetate (2×50 ml). The combined organic extracts were washed with brine (50 ml); dried over magnesium sulfate and evaporated in vacuo. The residue was purified using flash column chromatography (SiO2, ethyl acetate/petrol, 1:2 v/v) to give the title compound (50 mg, 79%) as a pale yellow gum. δH(CDCl3) 0.00 (6H, s), 0.06 (6H, s), 0.80 (9H, s), 0.83 (9H, s), 1.30-1.40 (4H, m), 1.70-1.75 (2H, m), 2.00-2.05 (2H, m), 2.60-2.70 (1H, m), 4.55-4.65 (1H, m), 6.10 (1H, d), 6.23 (1H, dd), 6.40 (1H, s), 6.76-7.20 (5H, m).
Reaction SMILES: CN(C=O)C.S(Cl)([Cl:8])=O.N1C=CC=CC=1.[CH2:16]([O:28][C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([O:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:36]=1)[CH2:32]O)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>ClCCl>[CH2:16]([O:28][C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([O:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:36]=1)[CH2:32][Cl:8])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCCCCCCCCOc1cc(CO)cc(OCCCCCCCCCCCC)c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCOc1cc(CCl)cc(OCCCCCCCCCCCC)c1
Reaction time: 0.17 h
Yield: 88.5 %

Procedure:
A 1 L RBF was prepared containing 5 mL dry dichloromethane, a stir bar, a septum, an out-vent line, and a nitrogen gas line. DMF (3.3 ml, 40.3 mmol) was added and the reaction mixture was cooled in an ice bath. Thionyl chloride (2.7 ml, 40.3 mmol) was added and the reaction mixture was allowed to stir for 10 minutes. The ice bath was then removed and the reaction was allowed to stir for an additional 10 minutes. The RBF was placed in the ice bath and a mixture of pyridine (2.72 ml, 33.6 mmol) and 3,5-didodecoxybenzyl alcohol (13.2 g, 33.6 mmol) were added and dissolved in approximately 50 mL dichloromethane, drop-wise through the septum. After 15 minutes, the RBF was removed from the ice bath and the reaction mixture was stirred for 2 hours. The reaction mixture was then placed in a refrigerator overnight. The solvent was removed by rotary evaporation. To the remaining organic matter, 100 mL of 50% ether/hexanes was added to dissolve the desired derivative. A solid orange precipitate formed, the remaining liquid was decanted off, and the precipitate was washed with an additional 100 mL 50% ether/hexanes. The combined organic liquid was vacuum filtered through silica gel into a RBF and the solvent was removed under reduced pressure. Trace solvent was removed by high vacuum overnight. There was a 10.2 g yield or a 88.5% yield. The NMR characterization data for the derivative is as follows. 1NMR (300 MHz, CDCl3): 0.87 (t, J=6.6, 6H, CH2CH3), 1.15-1.6 (m, 36H, CH2(CH2)9), 1.76 (p, J=8.0, 4H, OCH2CH2), 3.9 (t, J=6.6, 4H, OCH2CH2), 4.5 (s, 2H, ArCH2), 6.36 (t, J=2.2, 1H, ArH), 6.50 (d, J=2.2, 2H, ArH).
Reaction SMILES: [CH2:1]([C:5]1=[CH:6][N:7]([C:24]([CH3:27])([CH3:26])[CH3:25])[S:8]/[C:9]/1=[N:10]\[C:11]([C@:13]1([CH3:23])[CH2:17][CH2:16][C@H:15]([C:18]([OH:20])=O)[C:14]1([CH3:22])[CH3:21])=[O:12])[CH2:2][CH2:3][CH3:4].Cl.[CH3:29][NH2:30]>>[CH2:1]([C:5]1=[CH:6][N:7]([C:24]([CH3:26])([CH3:25])[CH3:27])[S:8]/[C:9]/1=[N:10]\[C:11]([C@:13]1([CH3:23])[CH2:17][CH2:16][C@H:15]([C:18]([NH:30][CH3:29])=[O:20])[C:14]1([CH3:22])[CH3:21])=[O:12])[CH2:2][CH2:3][CH3:4]
Reactant: CN
Reactant: CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)[C@]1(C)CC[C@H](C(=O)O)C1(C)C
Agent: Cl
Product: CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)[C@]1(C)CC[C@H](C(=O)NC)C1(C)C

Procedure:
The product from Example 173 and methylamine hydrochloride (Aldrich) were processed using the method described in Example 178 to afford the title compound. 1H NMR (DMSO-d6) δ 0.47 (s, 3H), 0.90 (t, J=7.3 Hz, 3H), 1.19 (s, 3H), 1.22 (s, 3H), 1.26-1.33 (m, 2H), 1.36-1.45 (m, 1H), 1.57 (s, 9H), 1.57-1.68 (m, 3H), 1.96-2.08 (m, 1H), 2.57 (d, J=4.7 Hz, 3H), 2.60-2.67 (m, 3H), 2.72-2.83 (m, 1H), 4.78 (q, J=4.5 Hz, 1H), 8.50 (s, 1H). MS (ESI+) m/z 408 (M+H)+. Anal. calcd. for C22H37N3O2S: C, 64.83; H, 9.15; N, 10.31. Found: C, 64.20; H, 9.03; N, 10.25.
Reaction SMILES: O.O.Cl[Sn]Cl.[NH4+].[Cl-].CO.C(O)[C@H:11]1[O:16][C@H:15]([O:17][C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H:14]([OH:29])[C@@H:13](O)[C@@H]1O>O>[C:15]([O:16][CH3:11])(=[O:17])[CH:14]([CH3:13])[OH:29].[C:15]([OH:17])(=[O:16])[CH:14]([CH3:13])[OH:29]
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Agent: Cl[Sn]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: CC(O)C(=O)O
Product: COC(=O)C(C)O
Temperature: 130 °C
Reaction time: 1.5 h

Procedure:
In the reaction, 100 g of SnCl2.2H2O and 200 g of NH4Cl were added into a reactor (inside volume 10.0 L) as catalyst. 3.0 kg of methanol was also added into the reactor. The reactor was sealed and heated to 130° C. under stirring. A solution of 0.500 kg sucrose in 0.800 kg water was pumped into the reactor with a flow of 10.0 mL/min to carry out the reaction. After pumping all of the sucrose solution into the reactor, the reaction was kept running for another 1.5 h to complete the reaction. The resulted solution was analyzed by GC and high-performance liquid chromatography (HPLC). 80.2% of total molar yield of methyl lactate and lactic acid was obtained. The reaction was reproduced and a total yield of methyl lactate and lactic acid of 95.0% was obtained.