Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:53])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][C:45]5[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=5)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][NH:24]1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=2[CH3:19])=[CH:8][CH:7]=1.[CH3:54][N:55]1[CH:59]=[CH:58][C:57]([C:60]([OH:62])=O)=[N:56]1>C(Cl)Cl>[Cl:52][C:47]1[CH:46]=[C:45]([CH:50]=[CH:49][C:48]=1[Cl:51])[CH2:44][O:43][C:40]1[CH:39]=[CH:38][C:37]([C@H:35]2[CH2:34][O:33][C:29]3=[CH:30][C:31]4[CH2:32][C@@H:23]([C:21]([NH:20][C@@H:4]([CH2:5][C:6]5[CH:11]=[CH:10][C:9]([C:12]6[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=6[CH3:19])=[CH:8][CH:7]=5)[C:3]([OH:53])=[O:2])=[O:22])[N:24]([C:60]([C:57]5[CH:58]=[CH:59][N:55]([CH3:54])[N:56]=5)=[O:62])[CH2:25][C:26]=4[CH:27]=[C:28]3[O:36]2)=[CH:42][CH:41]=1
Reactant: Cn1ccc(C(=O)O)n1
Reactant: COC(=O)[C@H](Cc1ccc(-c2ccnc(C)c2C)cc1)NC(=O)[C@@H]1Cc2cc3c(cc2CN1)O[C@@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)CO3
Solvent: ClCCl
Product: Cc1nccc(-c2ccc(C[C@H](NC(=O)[C@@H]3Cc4cc5c(cc4CN3C(=O)c3ccn(C)n3)O[C@@H](c3ccc(OCc4ccc(Cl)c(Cl)c4)cc3)CO5)C(=O)O)cc2)c1C

Procedure:
(S)-2-({(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (30 mg) was reacted with 1-methyl-1H-pyrazole-3-carboxylic acid in DCM (3.0 mL) according to General Procedure A and directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound (15 mg). LCMS (m/z): 847.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([NH2:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:18])[C:6]=2[C:5]([O:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])=[CH:4][CH:3]=1.N[C:26]1C2C(=O)C3C(=C(N)C=CC=3)C(=O)C=2C(Cl)=CC=1.CNN(NC)CCO.[Na].[CH3:53][O:54][S:55]([O:58]C)(=[O:57])=[O:56]>O.ClC1C=CC=CC=1>[CH3:53][O:54][S:55]([O-:58])(=[O:57])=[O:56].[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([NH2:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:18])[C:6]=2[C:5]([O:19][CH2:20][CH2:21][N+:22]([CH3:26])([CH3:24])[CH3:23])=[CH:4][CH:3]=1
Reactant: CN(C)CCOc1ccc(N)c2c1C(=O)c1c(N)cccc1C2=O
Reactant: Nc1cccc2c1C(=O)c1c(Cl)ccc(N)c1C2=O
Reactant: COS(=O)(=O)OC
Agent: CNN(CCO)NC
Agent: [Na]
Solvent: Clc1ccccc1
Solvent: O
Product: COS(=O)(=O)[O-]
Product: C[N+](C)(C)CCOc1ccc(N)c2c1C(=O)c1c(N)cccc1C2=O

Procedure:
6.6 parts of 1,5-diamino-4-(2-dimethylamino-ethoxy)-anthraquinone prepared from 1,5-diamino-4-chloro-anthraquinone, N,N-dimethylaminoethanolamine and metallic sodium at 95-120° C. were dispersed in 75 parts of chlorobenzene and treated with 1.4 parts of dimethylsulfate. The reaction mixture was kept for 1½ hours at room temperature. The precipitate was filtered off and stirred with 150 parts of water followed by filtration. The filtrate was evaporated in vacuo yielding 2.5 parts of the dye of formula Ik. The red dye Ik is very good water-soluble. The analytic data are consistent with the assigned structure for dye Ik.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:10]=[C:11]([S:18][CH3:19])[S:12][C:13]=1[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C(CC)CNC1N=CC=CC=1C(OCC)=[O:28])C.N>>[CH2:1]([N:8]1[C:9]2[N:10]=[C:11]([S:18][CH3:19])[S:12][C:13]=2[C:14](=[O:15])[O:16][C:17]1=[O:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cccnc1NCC(CC)CC
Reactant: COC(=O)c1sc(SC)nc1NCc1ccccc1
Agent: N
Product: CSc1nc2c(s1)c(=O)oc(=O)n2Cc1ccccc1

Procedure:
The title compound was prepared according to the procedure of Example 3B substituting the product of Example 139A for the product of Example 3A (0.048 g, 92%). MS (DCI/NH3) m/z 324 (M+NH4)+.
Reaction SMILES: [CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19](B4OC(C)(C)C(C)(C)O4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].Br[C:32]1[CH:33]=[CH:34][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[N:36][CH:37]=1>>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:32]4[CH:37]=[N:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][CH:33]=4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:11][CH2:12]1)=[O:6])([CH3:3])[CH3:2]
Reactant: CC(C)OC(=O)N1CCC(C2Cc3cc(B4OC(C)(C)C(C)(C)O4)ccc3O2)CC1
Reactant: CS(=O)(=O)c1ccc(Br)cn1
Product: CC(C)OC(=O)N1CCC(C2Cc3cc(-c4ccc(S(C)(=O)=O)nc4)ccc3O2)CC1
Yield: 66 %

Procedure:
The title compound is prepared from 4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester and 5-bromo-2-methanesulfonyl-pyridine following a procedure analogous to that described in Example 1.
Reaction SMILES: [C:1]([C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:8][N:7]([CH2:16][CH3:17])[C:6](=[O:18])[C:5]=1[N+:19]([O-])=O)(=[O:3])[CH3:2].N[C:23]1[O:27][N:26]=[C:25]([CH3:28])[CH:24]=1>C(O)C>[C:1]([C:4]1[C:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:8][N:7]([CH2:16][CH3:17])[C:6](=[O:18])[C:5]=1[NH:19][C:23]1[O:27][N:26]=[C:25]([CH3:28])[CH:24]=1)(=[O:3])[CH3:2]
Reactant: Cc1cc(N)on1
Reactant: CCn1nc(-c2ccccc2)c(C(C)=O)c([N+](=O)[O-])c1=O
Solvent: CCO
Product: CCn1nc(-c2ccccc2)c(C(C)=O)c(Nc2cc(C)no2)c1=O
Temperature: 50 °C
Reaction time: 96 h
Yield: 14.9 %

Procedure:
To a stirred solution of 200 mg (0.696 mmol) of 5-acetyl-2-ethyl-4-nitro-6-phenylpyridazin-3(2H)-one (Dal Piaz, V et al, J. Med. Chem. 1997, 40, 1417) in ethanol (10 mL), 5-amino-3-methylisoxazole (204 mg, 2.088 mmol) was added. The resulting mixture was stirred at 50° C. for four days. The solvent was evaporated and the residue purified by column chromatography (silica gel, hexane/ethyl acetate 2:1) to yield the title compound (35 mg, 14.9% yield).
Reaction SMILES: [Cl:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:5]=2[S:4][C:3]=1[C:14]([OH:16])=O.CN(C(ON1N=[N:32][C:27]2[CH:28]=[CH:29][CH:30]=[N:31][C:26]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:41](N(CC)C(C)C)(C)[CH3:42].CN(C=O)C>CO>[N:31]12[CH2:30][CH2:29][CH:28]([CH2:41][CH2:42]1)[C@@H:27]([NH:32][C:14]([C:3]1[S:4][C:5]3[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:6]=3[C:2]=1[Cl:1])=[O:16])[CH2:26]2
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: O=C(O)c1sc2cc([N+](=O)[O-])ccc2c1Cl
Reactant: CCN(C(C)C)C(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CO
Product: O=C(N[C@H]1CN2CCC1CC2)c1sc2cc([N+](=O)[O-])ccc2c1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
427 mg (1.66 mmol) of 3-chloro-6-nitro-1-benzothiophene-2-carboxylic acid, 300 mg (1.51 mmol) of R-3-aminoquinuclidine dihydrochloride, 687.4 mg (1.81 mmol) of HATU, 701 mg (5.43 mmol) of N,N-diisopropylethylamine and 4.0 ml of DMF are reacted according to the general procedure. 20 ml of methanol and 4 g of Dowex WX2-200 are added, and the mixture is stirred at RT for 1 h. The mixture is filtered and washed successively with water, methanol, methanol/trifluoroacetic acid 9:1 and methanol/trifluoroacetic acid 1:1. Evaporation of the filtrate gives 270 mg (49% of theory) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:5]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[C:14]([CH:16]=[CH:17][CH:18]=3)[NH2:15])=[CH:8][C:6]=2[N:7]=1.CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.Cl[C:42]([O:44][CH2:45][Cl:46])=[O:43]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]=[C:4]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[C:5]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[C:14]([NH:15][C:42](=[O:43])[O:44][CH2:45][Cl:46])[CH:16]=[CH:17][CH:18]=3)=[CH:8][C:6]=2[N:7]=1
Reactant: O=C(Cl)OCCl
Reactant: Nc1cccc(-c2cnc3c(N4CCOCC4)nc(Cl)nc3c2)c1
Agent: CN(C)c1cccc2cccc(N(C)C)c12
Solvent: ClC(Cl)Cl
Product: O=C(Nc1cccc(-c2cnc3c(N4CCOCC4)nc(Cl)nc3c2)c1)OCCl
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.3 %

Procedure:
To a 100 mL round bottom flask, 3-(2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)aniline (1.0 g, 0.0029 mol), 1,8-bis(dimethylamino)naphthalene (0.626 g, 0.0029 mol) and chloroform (60 mL) were added. The reaction mixture was cooled in an ice bath. To the same flask was added chloromethyl chloroformate (0.377 g, 0.0029 mol) and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with chloroform, washed with water and brine. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure to provide the title compound as a yellow solid (1.25 g, 98.4%). 1H NMR (400 MHz, DMSO-d6): δ 10.41 (br s, 1H), 9.07 (d, J=2.0 Hz, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.94 (br s, 1H), 7.62-7.51 (m, 3H), 6.01 (s, 2H), 4.98-3.98 (br s, 4H), 3.81 (t, J=4.4 Hz, 4H). LC-MS (ESI): Calculated mass: 433.07; Observed mass [M+H]+: 433.8 (RT: 1.63 min).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Br:11])[C:3]=1[CH3:12].[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[Br:13][CH2:12][C:3]1[C:2]([Br:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=1[Br:11]
Reactant: Cc1c(Br)cc([N+](=O)[O-])cc1Br
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=[N+]([O-])c1cc(Br)c(CBr)c(Br)c1
Temperature: 25 °C

Procedure:
A mixture of 2,6-dibromo-4-nitrotoluene (3.83 g, 1 eq.), N-bromosuccinimide (3.23 g, 1.4 eq.) and dibenzoylperoxide (315 mg, 0.1 eq.) in CCl4 was degassed with argon. The mixture was brought to reflux and azobisisobutyronitrile (213 mg, 0.1 eq.) was added. The mixture was maintained at reflux for 6 hours. The reaction was cooled to room temperature, concentrated and purified to give 1-Bromomethyl-2,6-dibromo-4nitrobenzene. 1H NMR (500 MHz, CDCl3) δ CHCl3: 4.81 (2H, s), 8.41(2H, s).
Reaction SMILES: [C:1]1([CH2:9][OH:10])[C:2]([CH2:7][OH:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.N1C=CN=C1.[C:16]([Si:20]([CH3:23])([CH3:22])Cl)([CH3:19])([CH3:18])[CH3:17]>CN(C)C=O.C(OCC)(=O)C>[Si:20]([O:8][CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH2:9][OH:10])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:23])[CH3:22]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCc1ccccc1CO
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCc1ccccc1CO
Temperature: 25 °C
Reaction time: 72 h
Yield: 41.9 %

Procedure:
To a solution of 1,2-benzenedimethanol (2 g) and imidazole (1.13 g) in N,N-dimethylformamide (30 mL) was added tert -butyldimethylchlorosilane (2.08 g), and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was washed with 1 mol/L hydrochloric acid, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=3/2) to give the title compound (1.46 g).
Reaction SMILES: [Br:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]([CH2:12][CH2:13][CH2:14][CH3:15])=[N:10][N:9]([C:16]3[CH:21]=[C:20]([C:22]([O:24]C)=O)[CH:19]=[CH:18][C:17]=3[Cl:26])[C:8]2=[O:27])=[C:4]([F:30])[CH:3]=1.C(Cl)Cl.CO>C(N)CCC>[Br:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]([CH2:12][CH2:13][CH2:14][CH3:15])=[N:10][N:9]([C:16]3[CH:21]=[C:20]([C:22](=[O:24])[NH:7][CH2:6][CH2:5][CH2:4][CH3:3])[CH:19]=[CH:18][C:17]=3[Cl:26])[C:8]2=[O:27])=[C:4]([F:30])[CH:3]=1
Reactant: CCCCc1nn(-c2cc(C(=O)OC)ccc2Cl)c(=O)n1Cc1ccc(Br)cc1F
Solvent: CO
Solvent: CCCCN
Solvent: ClCCl
Product: CCCCNC(=O)c1ccc(Cl)c(-n2nc(CCCC)n(Cc3ccc(Br)cc3F)c2=O)c1

Procedure:
A solution of 50 mg (0.10 mmol) of 4-(4-bromo-2-fluorobenzyl)-5-n-butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step D) in 1 mL of n-butylamine was stirred overnight at 65° C. and then evaporated in vacuo. The residue was flash chromatographed on 15 cc of silica gel (gradient elution with 1-5% MeOH in CH2Cl2) to yield 41 mg (76%) of colorless, glassy solid, mp 114°-116° C.; homogeneous by TLC (95:5 CH2Cl2 --MeOH); mass spectrum (FAB) M/e 537, 539 (M+1)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=O)[CH:2]=1.C(Cl)(=O)C([Cl:14])=O>ClCCl.CN(C)C=O>[ClH:14].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([Cl:14])=[O:10])[CH:2]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)Cc1cccnc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cl
Product: O=C(Cl)Cc1cccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3-Pyridylacetic acid (41 mg, 0.3 mmol) was dissolved in dry dichloromethane (1 mL), the solution was added with dimethylformamide (1 drop), and oxalyl chloride (0.03 mL, 0.36 mmol), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure to give 3-pyridylacetyl chloride hydrochloride. By using this compound and 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (63 mg, 0.2 mmol) obtained in Example 1, (3), the title compound (6.2 mg, yield 7%) was obtained as yellow amorphous in the same manner as that of Example 1, (4).
Reaction SMILES: C1([C@H]2OC(=O)N[C@@H]2C2C=CN=C(C#CC3C=CC=CN=3)C=2)C=CC=CC=1.Br[C:28]1[CH:29]=[C:30]([C@@H:34]2[C@@H:38]([C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=3)[O:37][C:36](=[O:46])[NH:35]2)[CH:31]=[N:32][CH:33]=1.C[Si]([C:51]#[C:52][C:53]1[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=1)(C)C>>[F:45][C:41]1[CH:40]=[C:39]([C@H:38]2[O:37][C:36](=[O:46])[NH:35][C@@H:34]2[C:30]2[CH:31]=[N:32][CH:33]=[C:28]([C:51]#[C:52][C:53]3[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=3)[CH:29]=2)[CH:44]=[CH:43][CH:42]=1
Reactant: O=C1N[C@H](c2cncc(Br)c2)[C@@H](c2cccc(F)c2)O1
Reactant: C[Si](C)(C)C#Cc1cccnc1
Agent: O=C1N[C@H](c2ccnc(C#Cc3ccccn3)c2)[C@@H](c2ccccc2)O1
Product: O=C1N[C@H](c2cncc(C#Cc3cccnc3)c2)[C@@H](c2cccc(F)c2)O1

Procedure:
Prepared according to the same procedure as (4R,5R)-5-phenyl-4-(2-(pyridin-2-ylethynyl)pyridin-4-yl)oxazolidin-2-one, starting with (4R,5R)-4-(5-bromopyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one and 3-((trimethylsilyl)ethynyl)pyridine. 1H-NMR (CDCl3, 500 MHz) δ 8.10-9.50 (bm, 3H), 7.94 (s, 1H), 7.88 (d, J=7.9, 1H), 7.42 (m, 2H), 7.10 (m, 3H), 6.81 (bs, 1H), 5.31 (d, J=7.3, 1H), 4.85 (d, J=7.3, 1H). 13C-NMR (CDCl3, 126 MHz) δ 164.2, 162.2, 158.4, 152.9, 147.4, 139.1 (d, J=6.7), 138.7, 136.5, 132.1 (d, J=11), 131.13, 131.06, 128.6 (d, J=12), 121.5 (d, J=3.8), 116.7 (d, J=21), 113.0 (d, J=23), 90.8, 88.5, 84.8, 62.5. Mass spec.: 360.0 (MH)+.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:7]=2[C:14]2[C:15]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:21]([CH3:31])=[C:20]([C:32](O)=[O:33])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:3][CH2:2]1.[NH2:35][C@@H:36]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]1>>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:7]=2[C:14]2[C:15]3[N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:30])[CH3:28])[C:21]([CH3:31])=[C:20]([C:32]([NH:35][C@@H:36]4[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]4)=[O:33])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:2][CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](N)C1
Reactant: COc1ccc(OCC2CC2)c(-c2ncnc3c(C(=O)O)c(C)n(COCC[Si](C)(C)C)c23)c1
Product: COc1ccc(OCC2CC2)c(-c2ncnc3c(C(=O)N[C@@H]4CCN(C(=O)OC(C)(C)C)C4)c(C)n(COCC[Si](C)(C)C)c23)c1

Procedure:
Starting from 4-[2-(cyclopropylmethoxy)-5-methoxyphenyl]-6-methyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (example D.c6) and commercially available tert-butyl(R)-3-amino-pyrrolidine-1-carboxylate the title compound is obtained as colorless foam.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][C:11]([NH:13][C:14]2[S:15][CH:16]=[C:17]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[N:18]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)([O-])=O.[NH4+].[OH-]>CN(C=O)C.CO.[Fe]>[NH2:1][C:4]1[CH:5]=[C:6]([CH2:10][C:11]([NH:13][C:14]2[S:15][CH:16]=[C:17]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[N:18]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1
Reactant: O=C(Cc1cccc([N+](=O)[O-])c1)Nc1nc(-c2c[nH]c3ncccc23)cs1
Agent: [Fe]
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Solvent: CN(C)C=O
Product: Nc1cccc(CC(=O)Nc2nc(-c3c[nH]c4ncccc34)cs2)c1
Temperature: 100 °C
Yield: 28.6 %

Procedure:
2-(3-Nitro-phenyl)-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-acetamide (200 mg, 0.5 mmol) was taken in DMF-MeOH (5 mL) and added to sat. NH4OH (5 ml) and Fe powder (3eq, 83 mg). Then the suspension was heated overnight at 100° C. The brown colored reaction mixture was passed through a celite plug and washed with ethyl acetate. Then the reaction mixture was concentrated to dryness and taken up in ethyl acetate and extracted with water. The organic layer was dried and concentrated to give the desired product as a tan solid (50 mg, 30% yield).
Reaction SMILES: [CH3:1][N:2]([CH3:30])[CH2:3][CH2:4][CH2:5][N:6]([C:21]1[C:26]([N+:27]([O-])=O)=[CH:25][CH:24]=[CH:23][N:22]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:14].[OH-].[Na+]>C(O)C.O.[Zn]>[CH3:30][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][N:6]([C:21]1[C:26]([NH2:27])=[CH:25][CH:24]=[CH:23][N:22]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:14]
Reactant: CN(C)CCCN(c1ccccc1C(=O)c1ccccc1)c1ncccc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Agent: [Zn]
Solvent: O
Solvent: CCO
Product: CN(C)CCCN(c1ccccc1C(=O)c1ccccc1)c1ncccc1N

Procedure:
A mixture of (0.05 mole) [2-[[3-(dimethylamino)propyl](3-nitro-2-pyridinyl)amino]phenyl]phenylmethanone, 13 g, (0.20 mole) of zinc dust, 2 g (0.05 mole) of sodium hydroxide in 75 ml ethanol and 25 ml water is stirred under reflux for 1 hr. The mixture is filtered and evaporated under reduced pressure. The residue is dissolved in methylene chloride and the resulting solution is dried over magnesium sulfate and decolorized with charcoal and filtered. The filtrate is evaporated to dryness and to give the title compound in crude mixture.
Reaction SMILES: C([O:4][CH2:5][CH2:6][N:7]([CH2:16][CH3:17])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][CH:9]=1)(=O)C.[C:18]1(=[O:24])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[OH-:25].[Na+]>C(O)C>[CH2:16]([N:7]([CH2:6][CH2:5][OH:4])[C:8]1[CH:9]=[CH:10][C:11]([CH:14]=[C:19]2[CH2:20][CH2:21][CH2:22][C:23](=[CH:14][C:11]3[CH:12]=[CH:13][C:8]([N:7]([CH2:6][CH3:5])[CH2:16][CH2:17][OH:25])=[CH:9][CH:10]=3)[C:18]2=[O:24])=[CH:12][CH:13]=1)[CH3:17]
Reactant: CCN(CCOC(C)=O)c1ccc(C=O)cc1
Reactant: O=C1CCCCC1
Reactant: [OH-]
Agent: [Na+]
Solvent: CCO
Product: CCN(CCO)c1ccc(C=C2CCCC(=Cc3ccc(N(CC)CCO)cc3)C2=O)cc1
Temperature: 50 °C
Yield: 185.2 %

Procedure:
23.5 g of 2-(ethyl(4-formylphenyl)amino)ethyl acetate, 4.91 g of cyclohexanone and 150 ml of ethanol were mixed and to this was added an aqueous solution (25 ml) of 2.2 g of sodium hydroxide while stirring at 50° C. This mixture was further stirred for 5 hours. After cooling to room temperature, a precipitate was filtrated, and washed with a small amount of ethanol and water to obtain 41.5 g of 2,6-bis((4-(ethyl(2-hydroxyethyl) amino)phenyl)methylene) cyclohexan-1-on e.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([S:13][CH2:14][C:15]([OH:17])=O)[S:11][CH:12]=2)=[CH:4][CH:3]=1.[CH:18]([NH:21][CH:22]([CH3:24])[CH3:23])([CH3:20])[CH3:19]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([S:13][CH2:14][C:15]([N:21]([CH:22]([CH3:24])[CH3:23])[CH:18]([CH3:20])[CH3:19])=[O:17])[S:11][CH:12]=2)=[CH:6][CH:7]=1
Reactant: CC(C)NC(C)C
Reactant: O=C(O)CSc1nc(-c2ccc(F)cc2)cs1
Product: CC(C)N(C(=O)CSc1nc(-c2ccc(F)cc2)cs1)C(C)C

Procedure:
The title compound was prepared analogously as described in Example 30(d) from 100 mg (0.37 mmol) of [4-(4-fluoro-phenyl)-thiazol-2-ylsulfanyl]-acetic acid and 75.1 mg (0.74 mmol) of diisopropylamine. Yield: 57 mg.
Reaction SMILES: [CH2:1]([C:4]([C@@H:6]([C@H:8]([C@H:19]([C@@H:21]([CH2:23][OH:24])[OH:22])[OH:20])[O:9][CH:10](OC(C)(C)C)[C:11]([OH:13])=[O:12])[OH:7])=[O:5])[CH:2]=[CH2:3]>[OH-].[Na+]>[CH2:1]([C:4]([C@@H:6]([C@H:8]([C@H:19]([C@@H:21]([CH2:23][OH:24])[OH:22])[OH:20])[O:9][CH2:10][C:11]([OH:13])=[O:12])[OH:7])=[O:5])[CH:2]=[CH2:3]
Reactant: C=CCC(=O)[C@H](O)[C@@H](OC(OC(C)(C)C)C(=O)O)[C@@H](O)[C@H](O)CO
Agent: [Na+]
Agent: [OH-]
Product: C=CCC(=O)[C@H](O)[C@@H](OCC(=O)O)[C@@H](O)[C@H](O)CO
Reaction time: 2 h
Yield: 113 %

Procedure:
Compound 7 (7.8 g) was dissolved in 2N NaOH solution and stirred for 2 hr. The reaction mixture was acidified with Dowex-H resin and the resin was removed by filtration. The filtrate was lyophilized to give 1-C-allyl-3-O- carboxymethylgalactose (7.0 g). 1H NMR (CD3OD) : δ, 2.38-2.42, 2H; 3.28-3.31, m, 1H; 3.44-3.47, dd, 2H; 3.63-3.67,m, 2H; 3.98-4.02, m, 1H; 4.11-4.15,m, 1H; 4.22-4.25,m, 1H; 4.95-5.00, and 5.10-5.15,dd, 2H, CH2CH=CH2 ; 5.75-5.85, m, 1H, CH2 CH=CH2 : 13C NMR (CD3OD) : 176.52 (COOH) ; 136.67, 116.89, 81.98, 79.79, 76.00, 73.50, 68.60, 68.56, 67.59, 62.05, 30.70: [α]D =+66.82 (c 0.214, methanol).
Reaction SMILES: [C@@H:1]1(N2C3N=CN=C(O)C=3N=C2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[NH:19]1[CH:27]=[C:25]([CH3:26])[C:23](=[O:24])[NH:22][C:20]1=[O:21]>C([O-])(=O)C.[NH4+]>[C@@H:1]1([N:19]2[CH:27]=[C:25]([CH3:26])[C:23](=[O:24])[NH:22][C:20]2=[O:21])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1
Reactant: Cc1c[nH]c(=O)[nH]c1=O
Reactant: OC[C@H]1O[C@@H](n2cnc3c(O)ncnc32)C[C@@H]1O
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reaction time: 1 h
Yield: 56 %

Procedure:
The assay mixture contained 2 g (wet weight) of Bacillus stearothermophilus cells, 5 mM 2′-deoxyinosine and 5 mM thymine in 10 ml of 50 mM ammonium acetate buffer (pH 5.5). The conversions were run at 55° C. for 1 hour. The reaction mixture was centrifuged and then filtered using an Amicon Ultrafiltration device (YM-3 membrane) and the products were separated and analyzed by HPLC (C-18 column) in 5% methanol and 5 mM phosphate buffer at pH 4.6 using a flow rate of 0.5 ml/min. Blanks were run to check the authenticity of the reaction. No undesirable side reactions were detected. Thymidine was obtained in 56% yield (78% conversion).
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[CH2:6]([O:8][C:9]([C:11]1[C:16](O)=[C:15]([CH3:18])[C:14](=[O:19])[N:13]([CH3:20])[C:12]=1[CH3:21])=[O:10])[CH3:7]>>[CH2:6]([O:8][C:9]([C:11]1[C:16]([Cl:3])=[C:15]([CH3:18])[C:14](=[O:19])[N:13]([CH3:20])[C:12]=1[CH3:21])=[O:10])[CH3:7]
Reactant: CCOC(=O)c1c(O)c(C)c(=O)n(C)c1C
Reactant: O=P(Cl)(Cl)Cl
Product: CCOC(=O)c1c(Cl)c(C)c(=O)n(C)c1C
Temperature: 80 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
Phosphorous oxychloride (20.0 mL, 216 mmol) was added to 4-hydroxy-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester and heated to 80° C. After two hours, the reaction mixture was concentrated under reduced pressure. The resulting residue was poured onto ice and, carefully neutralized with saturated NaHCO3, and diluted with EtOAc. After stirring for 16 hours, the organic layer was separated and the aqueous layer was reextracted with EtOAc repeatedly. The pH of the aqueous layer was adjusted to pH 11 with saturated K2CO3 and extracted with EtOAc (2×). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to give 3.42 g (89%) clean desired product.