Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4].[C:18]1([CH2:24][CH2:25]Br)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O>[C:3]([NH:6][C:7]([CH2:25][CH2:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4]
Reactant: CCOC(=O)C(NC(C)=O)C(=O)OCC
Reactant: BrCCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(CCc1ccccc1)(NC(C)=O)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of sodium hydride (50.6 g) in dimethylformamide (1500 ml) was dropwise added a solution of diethyl acetamidomalonate (250 g) in dimethylforamide (200 ml) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. 2-Phenylethyl bromide (156 ml) was dropwise added thereto and the resultant mixture was stirred for 7 hours at room temperature. The reaction mixture was poured into ice water (1500 ml) and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled away. The obtained residue was crystallized from toluene to give the title compound (102 g) as white crystals, melting point 115-117° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:16][CH:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH3:18])C(=O)OC(C)(C)C)[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([F:36])=[C:33]([CH:35]=1)[NH2:34].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([F:36])=[C:33]([NH:34][C:2]2[CH:7]=[C:6]([NH:8][CH2:16][CH:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[CH3:18])[N:5]3[N:25]=[CH:26][CH:27]=[C:4]3[N:3]=2)[CH:35]=1
Reactant: Nc1cc(Cl)ccc1F
Reactant: CC(CN(C(=O)OC(C)(C)C)c1cc(Cl)nc2ccnn12)N1CCOCC1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Product: CC(CNc1cc(Nc2cc(Cl)ccc2F)nc2ccnn12)N1CCOCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 20.7 %

Procedure:
To tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate (396 mg, 1 mmol), 5-chloro-2-fluoroaniline (145 uL, 1.2 mmol), and LiHMDS (2.2 mL, 2.2 mmol, 1M in THF) was added X-Phos (11 mg, 0.024 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.02 mmol). The mixture was sealed and irradiated at 65° C. for 60 min in the microwave. The reaction was quenched with 1N HCL (2 mL) and then neutralized with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude residue was dissolved in dichloromethane (2 mL) and trifluoroacetic acid (2 mL). After stirring at room temperature for 1 hour, the solution was concentrated under a stream of nitrogen. The crude material was neutralized with saturated sodium bicarbonate solution then purified by silica gel chromatography (75% ethyl acetate/hexanes) to yield the product, N5-(5-chloro-2-fluorophenyl)-N7-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine (84 mg, 21% yield). LCMS (M+1=405)
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1.[CH3:27][O:28][CH2:29][CH2:30][S:31](Cl)(=[O:33])=[O:32]>>[CH3:27][O:28][CH2:29][CH2:30][S:31]([N:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1)(=[O:33])=[O:32]
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(C2=CCNCC2)c(F)c1
Reactant: COCCS(=O)(=O)Cl
Agent: Cl
Product: COCCS(=O)(=O)N1CC=C(c2ccc(N3C[C@H](Cn4ccnn4)OC3=O)cc2F)CC1

Procedure:
(5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride (380 mg, 1 mM) was treated with 2-methoxyethylsulfonyl chloride essentially as in Example 79. Chromatography gave the desired product (65 mg).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33]C)=[O:32])[C:27]([CH3:36])([CH3:35])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.[OH-].[Na+]>CO>[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1
Reactant: COC(=O)[C@H]1CC[C@](O)(c2ncc(-c3cc(CN)cc(Nc4nccc(C(F)(F)F)n4)c3)s2)CC1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)C[C@@](O)(c2ncc(-c3cc(CN)cc(Nc4nccc(C(F)(F)F)n4)c3)s2)CC[C@@H]1C(=O)O
Yield: 36.3 %

Procedure:
A microwave vessel was charged with a solution of the compound of Step 3 (10 mg, 0.019 mmol) in MeOH, and sodium hydroxide (1.0 N in H2O, 56 μl, 0.056 mmol, 3 equiv) was added. The resultant cloudy orange suspension was irradiated in the microwave at 110° C. for 15 min. The reaction was not complete. Additional sodium hydroxide (1.0 N in H2O, 190 μL, 0.19 mmol, 10 eq) was added and the faintly yellow solution was irradiated at 150° C. for 30 min. The reaction mixture was concentrated in vacuo, then partitioned between diethyl ether (75 ml) and water (85 ml). The aqueous layer was acidified with 1N aqueous HCl to pH ˜3-4, then washed with EtOAc (2×35 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated, affording the title compound (3.6 mg, 35%) as an orange oil. MS ESI: [M+H]+ m/z 522.2 1H NMR (500 MHz, DMSO-d6) δ 10.5 (s, 1H), 8.85 (d, J=4.9 Hz, 1H), 8.24 (bs, 1H), 8.14 (s, 1H), 7.93 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.33 (d, J=4.9 Hz, 1H), 5.94 (bs, 1H), 4.03-3.99 (m, 3H), 3.14 (m, 2H), 2.19-2.16 (m, 2H), 1.86-1.83 (m, 2H), 1.66-1.60 (m, 2H), 1.17-1.11 (m, 6H). rhSYK activity=+++
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[C:8]([F:32])=[CH:7][C:5]=2[N:6]=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>N1C=CC=CC=1.C(OCC)(=O)C>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([O:11][C:9]2[C:8]([F:32])=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:36]([CH:33]4[CH2:35][CH2:34]4)=[O:37])[S:3][C:4]=3[CH:10]=2)[CH:13]=1)=[O:31])([CH3:28])[CH3:27])#[N:30]
Reactant: O=C(Cl)C1CC1
Reactant: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3cc4sc(N)nc4cc3F)c2)c1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3cc4sc(NC(=O)C5CC5)nc4cc3F)c2)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 51.2 %

Procedure:
To a solution of N-{3-[(2-amino-5-fluoro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.448 mmol) in pyridine (4.0 mL) was added cyclopropanecarbonyl chloride (61 μL, 0.672 mmol), and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed with 5% aqueous sodium hydrogencarbonate solution (100 mL) and saturated brine (100 mL), successively, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40→0/100), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether/hexane to give the title compound (118 mg, 51%) as a colorless solid.
Reaction SMILES: C(N1CC[O:11][C@H:10]([CH2:14][C:15]2C=CC=[C:17](C=CC3C=NC=CC=3)[CH:16]=2)C1)(OC(C)(C)C)=O.C([N:36]1[CH2:41][CH2:40][O:39][C@H:38]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[C:45]([Cl:50])[CH:44]=2)[CH2:37]1)(OC(C)(C)C)=O.C(O)C1OCCC1.C(O)(C(F)(F)F)=O>>[Cl:50][C:45]1[CH:44]=[C:43]([CH:48]=[CH:47][C:46]=1[O:49][CH2:17][CH:16]1[CH2:15][CH2:14][CH2:10][O:11]1)[CH2:42][C@H:38]1[O:39][CH2:40][CH2:41][NH:36][CH2:37]1
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](Cc2cccc(C=Cc3cccnc3)c2)C1
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](Cc2ccc(O)c(Cl)c2)C1
Solvent: OCC1CCCO1
Solvent: O=C(O)C(F)(F)F
Product: Clc1cc(C[C@@H]2CNCCO2)ccc1OCC1CCCO1

Procedure:
Example 52 was prepared using the same procedure as described for example 7 starting from example 7, intermediate (a), N-BOC-(R)-2-(3-chloro-4-hydroxybenzyl)morpholine and tetrahydrofurfuryl alcohol. The resulting intermediate was deprotected with TFA as described for example 7 to yield the desired morpholine example 52 as a colorless oil (26 mg, 52% over 2 steps) after purification by HPLC.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=O)[NH:5][CH:6]=[CH:7][CH:8]=1.P(Cl)(Cl)([Cl:12])=O.C(N(CC)C1C=CC=CC=1)C>O>[Cl:12][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][N:5]=1
Reactant: COc1ccc[nH]c1=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: O
Solvent: CCN(CC)c1ccccc1
Product: COc1cccnc1Cl

Procedure:
3-methoxy-2-(1H)pyridone, 10 g. (0.08 mole), 12.3 g. (0.08 mole) of phosphorus oxychloride, and 11.9 g. (0.08 mole) of N,N-diethylaniline are combined in a suitable reaction vessel and heated at reflux for 20 hrs. The reaction mixture was allowed to cool, and was then mixed with 200 ml. of water and ice. The aqueous mixture was extracted with ether and the extracts dried over magnesium sulfate. The drying agent was then removed by filtration and the solvent was removed from the filtrate by distillation in vacuo. The residue was extracted with 160 ml. of boiling hexane and the hexane extracts decanted from the residue while still hot. The hexane solution was cooled in ice resulting in precipitation of the desired produce, weight 7.5 g., m.p. 46°-48°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].I[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]([CH:25]([CH3:27])[CH3:26])[N:16]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.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>[CH:25]([N:17]1[C:18]2=[N:19][CH:20]=[N:21][C:22]([NH2:24])=[C:23]2[C:15]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:16]1)([CH3:27])[CH3:26]
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Reactant: COc1ccc(B(O)O)cc1OC
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: COCCOC
Solvent: CCO
Product: COc1ccc(-c2nn(C(C)C)c3ncnc(N)c23)cc1OC
Temperature: 80 °C
Yield: 59.7 %

Procedure:
A solution of 3,4-Dimethoxyphenylboronic acid (24 mg, 0.13 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (20 mg, 0.07 mmol) in DME (12 ml). Pd(PPh3)4 (16 mg, 0.014 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA23 (13.1 mg, 60% yield). ESI-MS (M+H)+ m/z calcd 314.0, found 314.1.
Reaction SMILES: [C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:15][C:16]([CH3:18])=O.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:16]([CH3:18])[CH3:15])[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)=O
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)N1CCC(NC(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Yield: 72.7 %

Procedure:
t-Butyl-piperidin-4-ylcarbamate (3 g, 15 mmol) obtained in Preparation Example 2-ii was dissolved in methanol (30 ml) in a 100 ml vessel, and acetone (7.70 ml, 105 mmol) and acetic acid (0.45 ml, 7.5 mmol) were added thereto while stirring. To the resulting mixture, NaCNBH3 (1.88 mg, 30 mmol) was added dropwise in 4-divided portions and reacted for 18 hrs. After the completion of reaction, ice water was poured to the reaction product while stirring, and the resulting mixture was extracted with ethyl acetate. The organic layer was separated, washed with an aqueous sodium bicarbonate solution and brine in order, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue thus obtained was subjected to a silica gel column chromatography to obtain 2.644 g of the title compound as a white solid (yield 73.3%).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[N:9]=[C:8]([NH2:10])[C:7]([CH:11]=[CH:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH3:14])=[C:6]([CH3:22])[N:5]=1)[CH3:2].[C:23](OC(=O)C)(=[O:25])[CH3:24]>CN(C)C1C=CN=CC=1>[CH2:1]([NH:3][C:4]1[N:9]=[C:8]([NH:10][C:23]([CH3:24])=[O:25])[C:7]([CH:11]=[CH:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH3:14])=[C:6]([CH3:22])[N:5]=1)[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCNc1nc(C)c(C=CC(C)c2ccc(Cl)cc2)c(N)n1
Agent: CN(C)c1ccncc1
Product: CCNc1nc(C)c(C=CC(C)c2ccc(Cl)cc2)c(NC(C)=O)n1

Procedure:
This compound is prepared in a manner analogous to that of Example 8, using 0.32 gram (0.001 mole) 2-ethylamino-4-amino-6-methyl-5-[3-(4-chlorophenyl)-1-butenyl]pyrimidine (Compound 47-prepared in Example 7) and 0.01 gram (catalyst) of 4-dimethylaminopyridine in 5 mL of acetic anhydride, yielding 2-ethylamino-4-methylcarbonylamino-6-methyl-5-[3-(4-chlorophenyl)-1-butenyl]pyrimidine.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.F[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1.[OH-].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[N+:21]([C:18]1[CH:19]=[CH:20][C:15]([O:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[CH:16][CH:17]=1)([O-:23])=[O:22]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](O)C1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: O
Product: CC(C)(C)OC(=O)N1CC[C@@H](Oc2ccc([N+](=O)[O-])cc2)C1
Temperature: 40 °C
Reaction time: 24 h

Procedure:
(R)-Tert-butyl 3-hydroxypyrrolidine-1-carboxylate (10 g, 53.4 mmol) was dissolved in 1-fluoro-4-nitrobenzene (13.94 g, 99 mmol). An aqueous solution of 5.9N potassium hydroxide (77 ml, 452 mmol) was added followed by addition of tetrabutylammonium bromide (2.238 g, 6.94 mmol). The reaction mixture was stirred at 40° C. for 24 hours, cooled, diluted with water and extracted with ethyl acetate. The combined organic layers were dried with sodium sulfate, filtered and concentrated to give the title compound.
Reaction SMILES: C(OP(O)(O)=O)[C@H:2]1[O:7][C@H:6]([OH:8])[C@@H:5]([OH:9])[C@@H:4]([OH:10])[C@@H:3]1[OH:11].[OH:17][CH2:18][C:19]([C@H:21]([C@H:23]([CH2:25][OH:26])[OH:24])[OH:22])=[O:20]>>[O:7]=[CH:2][C@H:3]([C@H:4]([C@H:5]([CH2:6][OH:8])[OH:9])[OH:10])[OH:11].[OH:17][CH2:18][C:19]([C@H:21]([C@H:23]([CH2:25][OH:26])[OH:24])[OH:22])=[O:20]
Reactant: O=P(O)(O)OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O
Agent: O=C(CO)[C@@H](O)[C@@H](O)CO
Product: O=C[C@@H](O)[C@@H](O)[C@@H](O)CO

Procedure:
As a result, in the case of mannose-6-phosphate isomerase derived from Thermus thermophiles strain, all of the conversion rates were approximately 70% regardless the concentrations of L-ribulose used as a substrate thereby producing 36, 71, 140, and 211 g/l of L-ribose at 50, 100, 200, and 300 g/l of L-ribulose, respectively.
Reaction SMILES: [CH2:1]([O:17][CH2:18][CH:19]([CH2:22][O:23][C:24]([C:37]1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:20][OH:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(OC(=O)C)(=[O:45])C>N1C=CC=CC=1>[CH2:1]([O:17][CH2:18][CH:19]([CH2:22][O:23][C:24](=[O:45])[CH3:37])[CH2:20][OH:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCOCC(CO)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCCOCC(CO)COC(C)=O
Yield: 84 %

Procedure:
A solution of compound 4 (2.80 g, 4.90 mmol) in acetic anhydride (5 ml) and pyridine (5 ml) was stirred at room temperature for 6 hours. The solution was concentrated and the oil was dissolved in 4:3:1 glacial acetic acid-ethanol-water (20 ml) and heated on a steam bath. After 2 hours the solution was concentrated and the residue was chromatographed on silica gel using 10% ethylacetatehexane to afford 1.53 g (84%) of the title compound (6) as a waxy white solid, m.p. 33°. NMR (CDCl3, (CH3)4Si); δ0.90 (t, 3H, J=6 Hz, --CH3), 1.25 (s, 26H, --CH2 --), 1.54 (m, 2H, --OCH2CH2R), 2.03 (s, 3H, CH3), 2.16 (m, 1H, CH), 2.54 (t, 1H, J=6.5 Hz, --OH), 3.41 (t, 3H, J=6.5 Hz, --OCH2R), 3.53, 3.56 (ABX, 2H, JAB =8.5, /J 5 Hz, --CH2OR), 3.73 (t, 2H, J=5 Hz, CH2OH), 4.18 (d, 2H, J=6.5 Hz, CH2OAc).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]([C:13]1[CH:14]=[C:15]([CH:25]=[CH:26][CH:27]=1)[O:16][CH2:17][CH2:18][CH2:19][C:20]([O:22]CC)=[O:21])[OH:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]([C:13]1[CH:14]=[C:15]([CH:25]=[CH:26][CH:27]=1)[O:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[OH:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CCCOc1cccc(C(O)CCNC(=O)OC(C)(C)C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCC(O)c1cccc(OCCCC(=O)O)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To the ester 130 (2.3 g, 6.0 mmol) in THF (80 mL) and MeOH (20 mL) was added NaOH solution (8 mL, 2N). The resulting mixture was stirred at room temperature for overnight following which the solvent was removed under reduced pressure and pH adjusted to 6 by the addition of cold dilute HCl. This was then extracted with DCM. The organic layer was washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give 4-(3-(3-(tert-butoxycarbonylamino)-1-hydroxypropyl)phenoxy)butanoic acid (131). The product was directly utilized for the next transformation. Yield (1.94 g, 91%): 1H NMR (400 MHz, CDCl3) δ 7.18-7.22 (m, 1H), 6.84-6.90 (m, 2H), 6.77 (dd, J=7.6, 1.6 Hz, 1H), 5.18 (bs, 1H), 4.48-4.53 (m, 1H), 3.96 (t, J=6.4 Hz, 2H), 2.93-2.99 (m, 2H), 2.38 (t, J=7.4 Hz, 2H), 1.90-1.96 (m, 2H), 1.64-1.71 (m, 2H), 1.45 (s, 9H).
Reaction SMILES: [CH:1]1([N:5]2[C:10]([NH2:11])=[C:9]([NH2:12])[C:8](=[O:13])[NH:7][C:6]2=[O:14])[CH2:4][CH2:3][CH2:2]1.[C:15](O)(=O)[CH3:16]>>[CH:1]1([N:5]2[C:10]3[N:11]=[C:15]([CH3:16])[NH:12][C:9]=3[C:8](=[O:13])[NH:7][C:6]2=[O:14])[CH2:2][CH2:3][CH2:4]1
Reactant: Nc1c(N)n(C2CCC2)c(=O)[nH]c1=O
Reactant: CC(=O)O
Product: Cc1nc2c([nH]1)c(=O)[nH]c(=O)n2C1CCC1

Procedure:
A solution of 2.2 g of 1-cyclobutyl-5,6-diamino-2,4-(1H,3H)-pyrimidinedione (X) in 10 ml of acetic acid was refluxed for 2 hours. The solution was evaporated. The received oil was refluxed in 30 ml of 5N NaOH for 1 hour and then neutralized with 5 N HCl. The crystals were filtered off and recrystallized from 100 ml ethanol. Yield 0.4 g (18%) (XXXVII) NMR (see Table I).
Reaction SMILES: [Na].Cl[C:3]1[N:8]=[C:7]([C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:6]=[C:5]([NH:15][S:16]([CH:19]=[CH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:18])=[O:17])[C:4]=1[O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][CH3:35].Cl.[CH2:37]([OH:41])[CH2:38][CH2:39][OH:40]>>[OH:40][CH2:39][CH2:38][CH2:37][O:41][C:3]1[N:8]=[C:7]([C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:6]=[C:5]([NH:15][S:16]([CH:19]=[CH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:18])=[O:17])[C:4]=1[O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][CH3:35]
Reactant: OCCCO
Reactant: COc1ccccc1Oc1c(Cl)nc(-c2ncccn2)nc1NS(=O)(=O)C=Cc1ccccc1
Agent: Cl
Agent: [Na]
Product: COc1ccccc1Oc1c(NS(=O)(=O)C=Cc2ccccc2)nc(-c2ncccn2)nc1OCCCO
Temperature: 25 °C
Reaction time: 0.83 h
Yield: 80.5 %

Procedure:
Sodium (1.031 g) was dissolved in 20.130 g of 1,3-propanediol and 2.091 g of N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-2-phenylethenesulfonamide was added thereto with stirring at room temperature. The reaction mixture was stirred at room temperature for 50 minutes and then at 60° C. for 50 minutes and poured into a mixture of 1N hydrochloric acid and ice. This was extracted with ethyl acetate and the ethyl acetate layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the resulting residue was purified by a silica gel column chromatography (chloroform-methanol=100:1 to 20:1). The resulting syrup was crystallized in ether and collected by filtration to give 1.817 g of N-[6-(3-hydroxypropyloxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-2-phenylethenesulfonamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Br[CH2:11][CH2:12][CH2:13][OH:14].[OH-].[Na+].Cl>CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:11][CH2:12][CH2:13][OH:14])=[CH:5][CH:4]=1
Reactant: OCCCBr
Reactant: COc1ccc(O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: COc1ccc(OCCCO)cc1
Reaction time: 0.75 h

Procedure:
To a solution of 4-methoxyphenol (1.24 g) and 3-bromopropanol (1.18 ml) in DMSO (15 ml) was added in one portion powdered sodium hydroxide (1.12 g). The mixture was stirred for 0.75 h then poured into 2N hydrochloric acid (100 ml) and extracted with ethyl acetate (100 ml). The organic phase was washed with water (100 ml), dried and concentrated to give the title compound (1.785 g) as a pale brown solid, m.p. 56°-60°.
Reaction SMILES: [CH:1]1([CH3:11])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([OH:10])[CH2:2]1.[CH3:12][CH:13]1[CH2:18][C@H:17]([OH:19])[C@@H:16]([CH:20]([CH3:22])[CH3:21])[CH2:15][CH2:14]1.C(OC=C)(=O)C>CCCCCCC>[C:17]([O:10][CH:3]1[CH:4]([CH:7]([CH3:8])[CH3:9])[CH2:5][CH2:6][CH:1]([CH3:11])[CH2:2]1)(=[O:19])[CH3:16].[CH:13]1([CH3:12])[CH2:14][CH2:15][CH:16]([CH:20]([CH3:21])[CH3:22])[CH:17]([OH:19])[CH2:18]1
Reactant: CC1CC[C@H](C(C)C)[C@@H](O)C1
Agent: CC1CCC(C(C)C)C(O)C1
Solvent: CCCCCCC
Solvent: C=COC(C)=O
Product: CC(=O)OC1CC(C)CCC1C(C)C
Reaction time: 24 h

Procedure:
Lyophilised “AMANO AK” (a Pseudomonas fluorescens lipase enzyme) was obtained from Amano Pharmaceutical Co. (Japan). Concentrated liquid menthol was produced by the hydrogenation of thymol. The menthol contained four diastereomeric pairs of menthols, namely (+)-menthol (51%), (±)-isomenthol (14%), (±)-neomenthol (29%) and (±)-neoisomenthol (2%). A volume of 1 ml was added to sealed batch reactors. Vinyl acetate (54 μl) was added at a 2:1 molar ratio to (−)-menthol. Heptane was added as solvent to a final reaction volume of 5 ml. These reactors were incubated in silicon oil baths at 50° C. and stirred on a stirring hot plate. Batch times, unless otherwise stated were 24 hours. The reaction mixture was then centrifuged to separate the products from the enzyme. The supernatant was analysed by GC (% m/m analysis). Of the available (−)-menthol, 100% was converted to (−)-menthyl acetate, at an ee of 98%. The enzyme was recycled a total of 150 times by washing with heptane and adding fresh substrate (liquid menthol, vinyl acetate and heptane) after every recycle. An amount of menthyl acetate equivalent to 185 g of (−)-menthol was produced by this process.