Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([O-:3])=[O:2].CN(P(N(C)C)(N(C)C)=O)C.[Li]CCCC.[C:27]([O:31][C:32](=[O:40])[N:33]([CH:35]([CH3:39])[CH2:36][CH2:37]Br)[CH3:34])([CH3:30])([CH3:29])[CH3:28]>O1CCCC1>[C:27]([O:31][C:32](=[O:40])[N:33]([CH3:34])[CH:35]([CH3:39])[CH2:36][CH2:37][CH:4]([N+:1]([O-:3])=[O:2])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([CH3:29])([CH3:30])[CH3:28]
Reactant: CC(CCBr)N(C)C(=O)OC(C)(C)C
Reactant: O=[N+]([O-])Cc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CC(CCC(c1ccccc1)[N+](=O)[O-])N(C)C(=O)OC(C)(C)C
Temperature: -15 °C
Reaction time: 0.75 h
Yield: 28.1 %

Procedure:
To a −78° C. solution of 304 mg (2.219 mmol) nitromethyl-benzene (CAS: 622-42-4) in 5 ml tetrahydrofuran over mol-sieve and 1.29 ml HMPA, was added dropwise 2.91 ml (4.654 mmol) n-BuLi (1.6 M in hexane). After 45 minutes at −78° C., a solution of 590.7 mg (2.219 mmol) (3-bromo-1-methyl-propyl)-methyl-carbamic acid tert-butyl ester in 1.5 ml tetrahydrofuran over mol-sieve was added dropwise. After 1 hour at −78° C., the reaction mixture was allowed to warm up slowly, during 2 hours, to −15° C. The mixture was then cooled again to −78° C. and quenched with 0.75 ml of acetic acid, then with 13 ml saturated ammonium chloride. Back to room temperature, the aqueous phase was extracted two times with ethylacetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica (Eluent: heptane/ethyl acetate 0 to 10%) to provide 201 mg (28%) of the title compound as a colorless oil. MS (m/e): 323.3 (M+H).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[F:18])[N:14]=[C:13]([N:19]1[CH:23]=[C:22]([C:24]([O:26]CC)=[O:25])[CH:21]=[N:20]1)[NH:12][C:11]2=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30]([NH:32][CH2:33][CH3:34])[CH3:31]>>[CH2:1]([C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[F:18])[N:14]=[C:13]([N:19]1[CH:23]=[C:22]([C:24]([OH:26])=[O:25])[CH:21]=[N:20]1)[N:12]=[C:11]2[N:32]([CH2:33][CH3:34])[CH2:30][CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cnn(-c2nc3cc(F)c(Cc4ccccc4)cc3c(=O)[nH]2)c1
Reactant: CCNCC
Product: CCN(CC)c1nc(-n2cc(C(=O)O)cn2)nc2cc(F)c(Cc3ccccc3)cc12

Procedure:
The above compound may be made analogous to Example 1 using ethyl 1-(6-benzyl-7-fluoro-4-oxo-3,4-dihydroquinazolin-2-yl)-1H-pyrazole-4-carboxylate in step D and diethylamine in step E. MS (ESI): predicted mass calcd. for C23H22FN5O2, 419.2
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[C:3]=1[OH:11].[Br:12]Br>C(O)(=O)C.O>[Br:12][C:9]1[CH:10]=[C:2]([F:1])[C:3]([OH:11])=[C:4]([CH:8]=1)[C:5]([OH:7])=[O:6]
Reactant: O=C(O)c1cccc(F)c1O
Reactant: BrBr
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)c1cc(Br)cc(F)c1O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
5.00 g (32 mmol) of 3-fluorosalicylic acid was suspended in 50 ml of glacial acetic acid. 2.2 ml of bromine were added and the mixture was stirred at ambient temperature for 48 h. The resulting suspension was diluted with 500 ml of water and the precipitate filtered off and dried by suction to afford 9.394 g of 5-bromo-3-fluoro-2-hydroxybenzoic acid as an ivory solid.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:41])=[C:4]([C@@H:12]([NH:19][C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[C:24]2[CH:29]=[C:28]([NH:30][C:31]3[NH:32][CH2:33][CH:34]([OH:37])[CH2:35][N:36]=3)[CH:27]=[C:26]([OH:38])[CH:25]=2)[CH2:13][C:14]([O:16]CC)=[O:15])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.C(#N)C.O.O.[OH-].[Li+]>O.C(#N)C>[Br:1][C:2]1[C:3]([OH:41])=[C:4]([C@@H:12]([NH:19][C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[C:24]2[CH:29]=[C:28]([NH:30][C:31]3[NH:36][CH2:35][CH:34]([OH:37])[CH2:33][N:32]=3)[CH:27]=[C:26]([OH:38])[CH:25]=2)[CH2:13][C:14]([OH:16])=[O:15])[CH:5]=[C:6]([C:8]([CH3:9])([CH3:10])[CH3:11])[CH:7]=1
Reactant: CCOC(=O)C[C@H](NC(=O)CNC(=O)c1cc(O)cc(NC2=NCC(O)CN2)c1)c1cc(C(C)(C)C)cc(Br)c1O
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: CC(C)(C)c1cc(Br)c(O)c([C@H](CC(=O)O)NC(=O)CNC(=O)c2cc(O)cc(NC3=NCC(O)CN3)c2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 58.6 %

Procedure:
To a suspension of crude (3S)-ethyl 3-(3-bromo-5-(tert-butyl)-2-hydroxyphenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate (1.389 g, 2.19 mmol) in a 1:1 mixture of acetonitrile/water (10.0 mL) was added lithium hydroxide monohydrate (0.735 g, 17.51 mmol) at room temperature and the reaction mixture was stirred at room temperature for 3 h to afford a pale yellow solution. Acetonitrile was evaporated on a rotary evaporator to give a pale yellow aqueous residue. The residue was extracted with dichloromethane (2×25 mL) to remove HOBt and DIPU. The aqueous layer was neutralized with TFA (3.0 mL in 5.0 mL CH3CN) and the mixture was evaporated in vacuo to give a pale viscous residue. The crude product was purified by reverse-phase HPLC on Biotage SP1 system using a gradient 10-40% CH3CN in water containing 0.05% TFA to afford a colorless glassy solid. The purified product was dissolved in water containing a few drops of acetonitrile and lyophilized to afford a colorless powder (778.0 mg). LC/MS analysis of the purified product shows the desired product's mass: m/z 606 (79BrM+H) and m/z 608 (81BrM+H), Calc'd for C26H32BrN5O7: 606.466. 1H NMR (400 MHz, DMSO-d6): δ 1.25 (s, 9H, (CH3)3C—), 2.70 (ABq, JAB=16.00 and 8.73 Hz and JAB=15.95 and 5.45 Hz, 2H, —CH2—COOH), 3.17 (d, J=12.0 Hz, 2H), 3.35 (d, J=11.0 Hz, 2H), 3.89 (d, J=6.0 Hz, 2H), 4.09 (M, 1H), 5.45 (brm, 1H, —NH—CH—CH2—COOH), 6.75 (brt/m, J=2.02 Hz, 1H), 7.13 (dt, 2H), 7.26 (d, J=2.30 Hz, 1H), 7.34 (d, J=2.32 Hz, 1H), 8.60 (d, J=8.26 Hz, 1H), 8.64 (t, J=5.85 Hz, 1H), 9.31 (s, 1H), 9.60 (s, 1H), 10.02 (brs, 1H), 12.27 (brs, 1H, —COOH). 1H NMR spectrum of the sample was consistent with the suggested structure of the product.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:3][CH2:2]1.[CH3:21][CH:22]([CH3:32])[CH2:23][CH:24]([C:26]1[N:27]=[N:28][CH:29]=[CH:30][CH:31]=1)[NH2:25]>CCCCCCC.C(O)C.CC(O)C>[CH3:21][CH:22]([CH3:32])[CH2:23][C@H:24]([NH:25][C:12]([C:10]1[CH:9]=[CH:8][C:7]([N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[N:11]=1)=[O:14])[C:26]1[N:27]=[N:28][CH:29]=[CH:30][CH:31]=1
Reactant: O=C(O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1
Reactant: CC(C)CC(N)c1cccnn1
Solvent: CCCCCCC
Solvent: CC(C)O
Solvent: CCO
Product: CC(C)C[C@H](NC(=O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1)c1cccnn1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 69 b) and 3-methyl-1-(pyridazin-3-yl)butan-1-amine (Example 321 a) as starting materials. The product was isolated by chiral chromatography on Reprosil Chiral NR using a mixture of heptane, ethanol and 2-propanol as eluent. The (−)-enantiomer was isolated. MS (EI): m/e=432.5 [M+H]+.
Reaction SMILES: C(N)C1C=CC=CC=1.O1CC1COC1C2C3C(=CC=CC=3)NC=2C=CC=1.[CH3:27][O:28][C:29]1[C:34]([O:35][CH2:36][CH2:37][N:38]([CH2:46][CH:47]([OH:63])[CH2:48][O:49][C:50]2[C:55]3[C:56]4[C:61]([NH:62][C:54]=3[CH:53]=[CH:52][CH:51]=2)=[CH:60][CH:59]=[CH:58][CH:57]=4)CC2C=CC=CC=2)=[CH:33][CH:32]=[CH:31][CH:30]=1>[Cl-].[Cl-].[Zn+2].C1OCCOC1>[CH3:27][O:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][NH:38][CH2:46][CH:47]([OH:63])[CH2:48][O:49][C:50]1[CH:51]=[CH:52][CH:53]=[C:54]2[NH:62][C:61]3[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=3[C:55]=12
Reactant: COc1ccccc1OCCN(Cc1ccccc1)CC(O)COc1cccc2[nH]c3ccccc3c12
Agent: [Cl-]
Agent: [Zn+2]
Agent: c1ccc2c(c1)[nH]c1cccc(OCC3CO3)c12
Solvent: NCc1ccccc1
Solvent: C1COCCO1
Product: COc1ccccc1OCCNCC(O)COc1cccc2[nH]c3ccccc3c12
Reaction time: 10 h

Procedure:
To 5 ml Dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 0.21 g (0.0015 moles) of anhydrous ZnCl2 and 1 g (0.0042 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 2.5 hrs (TLC control for checking conversion to N-benzyl carvedilol). The dioxane is distilled off from the reaction mixture and to the concentrated mass is added 10 ml ethylacetate, followed by 2 ml of ˜12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4.5 Kg/cm2 at temperature of 60-70° C. for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.8 g).
Reaction SMILES: [CH:1]([N-:4]C(C)C)(C)C.[Li+].C(#N)C.[N:12]1([CH2:18][CH2:19][O:20][C:21]2[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=2)[C:24](OC)=O)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.O>O1CCCC1>[N:12]1([CH2:18][CH2:19][O:20][C:21]2[CH:22]=[C:23]([CH2:24][C:1]#[N:4])[CH:28]=[CH:29][CH:30]=2)[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1
Reactant: CC(C)[N-]C(C)C
Reactant: COC(=O)c1cccc(OCCN2CCOCC2)c1
Agent: [Li+]
Solvent: CC#N
Solvent: O
Solvent: C1CCOC1
Product: N#CCc1cccc(OCCN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Lithium diisopropylamide (18.8 ml, 37 mmol, 2.0 M solution in heptane/tetrahydrofuran/ethylbenzene) was added dropwise to a solution of acetonitrile (1.58 g, 37 mmol) in dry tetrahydrofuran (50 ml) at −78° C. After stirring the reaction mixture for 30 min., a solution of methyl 3-(2-morpholin-4-ylethoxy)benzoate in dry tetrahydrofuran (50 ml) was added dropwise over 10 min. After 15 min., water was added and the reaction mixture was allowed to warm to room temperature. The aqueous layer was separated and acidified with dilute hydrochloric acid to pH 7. The product was extracted into ethyl acetate and washed with water and brine and dried over magnesium sulfate. The organics were removed in vacuo to give 2-[3-(2-morpholin-4-ylethoxy)phenyl]acetonitrile (5.0 g) as an oil which was used in the next step without further purification.
Reaction SMILES: [OH:1][N:2]1C(=O)C2=CC=CC=C2C1=O.Br[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:24])=[O:23]>>[C:25]1([S:22]([CH2:21][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][O:1][NH2:2])(=[O:24])=[O:23])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: O=S(=O)(Cc1ccccc1CBr)c1ccccc1
Product: NOCc1ccccc1CS(=O)(=O)c1ccccc1

Procedure:
Prepared by the same procedure as described for preparation 15, starting from N-hydroxyphthalimide and 1-(bromomethyl)-2-[(phenylsulfonyl)methyl]benzene (Aldrich).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18])=[O:4].[Na+].[I-:21]>CC(C)=O>[I:21][CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18])=[O:4]
Reactant: COc1cc(COC(=O)CBr)c([N+](=O)[O-])cc1OC
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COc1cc(COC(=O)CI)c([N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 4.5-dimethoxy-2-nitrobenzyl 2-bromoacetate (100 mg, 0.3 mmol) was dissolved in acetone (2 ml) and NaI (50 mg, 0.33 mmol) was added. After stirring for two hours at room temperature, mixture was filtered, evaporated and purified by chromatography (Si-gel, CH2Cl2) to yield 4.5-dimethoxy-2-nitrobenzyl 2-iodoacetate (compound E (see FIG. 12c): P6—C1[X═I]) (97 mg, 85%).
Reaction SMILES: [CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Br[C:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45]([NH2:52])=[N:44][CH:43]=1>>[NH2:52][C:45]1[C:46]2[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:42]([C:5]2[N:4]=[C:3]3[C:8]([N:9]=[C:10]([CH2:11][N:12]4[CH2:13][CH2:14][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:16][CH2:17]4)[N:2]3[CH3:1])=[C:7]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[N:6]=2)=[CH:43][N:44]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nc(N2CCOCC2)c2nc(CN3CCC(C(C)(C)O)CC3)n(C)c2n1
Reactant: Nc1ncc(Br)c2ccccc12
Product: Cn1c(CN2CCC(C(C)(C)O)CC2)nc2c(N3CCOCC3)nc(-c3cnc(N)c4ccccc34)nc21

Procedure:
2-(1-((9-Methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (0.1 g) was reacted with 4-bromoisoquinolin-1-amine via General Procedure G to afford 115 following reverse phase purification. MS (Q1) 517.3 (M)+. 1H NMR (400 MHz, DMSO) δ 9.01 (d, 1H), 8.56 (s, 1H), 8.25 (d, 1H), 7.67 (t, 1H), 7.49 (t, 1H), 7.07 (s, 2H), 4.23 (s, 4H), 4.02 (s, 1H), 3.87-3.66 (m, 10H), 2.89 (d, 3H), 1.99 (t, 2H), 1.66 (d, 2H), 1.35-1.10 (m, 3H), 1.02 (s, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH:5]=[O:6].[Br-].Cl.[CH3:13][CH2:14]OC(C)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]([OH:6])[CH:13]=[CH2:14])[CH:7]=[C:8]([Cl:10])[CH:9]=1
Reactant: CCOC(C)=O
Reactant: O=Cc1cc(Cl)cc(Cl)c1
Agent: Cl
Agent: [Br-]
Solvent: C1CCOC1
Product: C=CC(O)c1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 3,5-dichlorobenzaldehyde (7.5 g, 43 mmol) in THF (75 mL) was cooled to 0° C. and vinylmagnesiuin bromide (1M in THF, 48 mL, 48 mmol) was added dropwise. The reaction was warmed to room temperature and was stirred overnight. Aqueous HCl (1N) and EtOAc were added. The aqueous solution was extracted with EtOAc and the organic solution was dried (MgSO4), filtered, and concentrated. The residue was used in the next step without further purification.
Reaction SMILES: [CH3:1][CH:2]([C@@H:15]1[C@:32]2([CH3:33])[C@H:18]([C:19]3[C@H:29]([CH2:30][CH2:31]2)[C@:27]2([CH3:28])[C:22]([CH2:23][C@@H:24]([O:39]C(OC)=O)[CH2:25][C@@H:26]2[O:34]C(OC)=O)=[CH:21][CH:20]=3)[CH2:17][CH2:16]1)[CH2:3]OS(C1C=CC(C)=CC=1)(=O)=O.[Li].C([Cu]CCC(C)C)CC(C)C.[CH2:56]([Li])[CH2:57][CH:58]([CH3:60])[CH3:59].[Cl-].[NH4+]>C(OCC)C>[CH3:59][CH:58]([CH2:57][CH2:56][CH2:3][C@H:2]([C@@H:15]1[C@:32]2([CH3:33])[C@H:18]([C:19]3[C@H:29]([CH2:30][CH2:31]2)[C@:27]2([CH3:28])[C:22]([CH2:23][C@@H:24]([OH:39])[CH2:25][C@@H:26]2[OH:34])=[CH:21][CH:20]=3)[CH2:17][CH2:16]1)[CH3:1])[CH3:60]
Reactant: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)COS(=O)(=O)c5ccc(C)cc5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Reactant: [Li]CCC(C)C
Agent: CC(C)CC[Cu]CCC(C)C
Agent: [Cl-]
Agent: [Li]
Solvent: CCOCC
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of 51 mg of 20-methyl-1α,3β-bis(methoxycarbonyloxy)-21-p-toluenesulfonyloxypregna-5,7-diene in 1 ml of diethyl ether was added dropwise, at -50° C. to -60° C., to a diethyl ether solution of diisoamylcopper lithium as prepared from 100 mg of cuprous iodide and 0.9 ml of 1.1N diethyl ether solution of isoamyllithium in 2 ml of diethyl ether. reaction mixture was poured into a cold aqueous solution of ammonium chloride and the resulting mixture was extracted with diethyl ether. The extract was washed with 10% aqueous ammonia, water and an aqueous solution of sodium chloride, dried over sodium sulfate and then concentrated. The residue was dissolved in 1 ml of methanol, 10 mg of potassium carbonate was added, and the resulting mixture was stirred at ambient temperature for 12 hours. The reaction mixture was poured into water and extracted with methylene chloride. The extract was washed with an aqueous solution of sodium chloride, dried over sodium sulfate and concentrated. The residue was washed with cold ethyl acetate to give 29 mg of cholesta-5,7-diene-1α,3β-diol.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=2[N+:17]([O-])=O)[CH:5]=[CH:6][CH:7]=1.[Cl-].[NH4+].O.O.O.O.O.O.O.O.O.[S-2].[Na+].[Na+]>CO>[NH2:17][C:10]1[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:9]=1[NH:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([I:1])[CH:3]=1
Reactant: N#Cc1ccc(Nc2cccc(I)c2)c([N+](=O)[O-])c1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: N#Cc1ccc(Nc2cccc(I)c2)c(N)c1
Temperature: 0 °C
Yield: 93 %

Procedure:
To a suspension of (29): (2.1 g, 5.75 mmol) in methanol (50 ml) is added ammonium chloride (0.92 g, 17.25 mmol) and sodium sulfide nonahydrate (4.14 g, 17.25 mmol) and the mixture is heated to reflux for 1.5 hours. After cooling the mixture is poured into ice-water (200 ml) and the product is filtered off, washed with water and dried to leave 1.8 g (93%) of the title compound. Mp. 170-172° C.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([OH:34])=O)=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.[CH3:44][C@@H:45]1[NH:50][CH2:49][CH2:48][N:47]([S:51]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([F:63])([F:62])[F:61])=[CH:56][CH:55]=2)(=[O:53])=[O:52])[CH2:46]1>CN(C=O)C>[Cl:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([N:50]2[CH2:49][CH2:48][N:47]([S:51]([C:54]3[CH:55]=[CH:56][C:57]([C:60]([F:63])([F:61])[F:62])=[CH:58][CH:59]=3)(=[O:52])=[O:53])[CH2:46][C@@H:45]2[CH3:44])=[O:34])=[CH:28][CH:27]=1
Reactant: C[C@H]1CN(S(=O)(=O)c2ccc(C(F)(F)F)cc2)CCN1
Reactant: O=C(O)c1ccc(Cl)nc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C[C@H]1CN(S(=O)(=O)c2ccc(C(F)(F)F)cc2)CCN1C(=O)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 98 %

Procedure:
HATU (458 mg, 1.21 mmol) was added to a solution of 6-chloro-3-pyridinecarboxylic acid (supplied by Aldrich) (174 mg, 1.10 mmol) in DMF (4 ml) and the mixture was treated with DIPEA (0.437 ml, 2.50 mmol). This mixture was stirred for ca. 10 min at ambient temperature. (3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 2) (308 mg, 1.0 mmol) was added and stirring was continued for 1.25 h. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3 solution (20 ml each). The layers were separated and the aqueous layer was washed with further DCM (2×20 ml). The combined organic layers were concentrated to leave a dark brown gum. Purification by silica chromatography (Biotage SP4, 25S cartridge), eluting with 12-100% ethyl acetate in pentane, gave the title compound (439 mg) as a pale yellow gum.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:5]([C:7]1[N:8]=[CH:9][N:10]([CH3:12])[CH:11]=1)=[O:6].[Cl:19][C:20]1[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O.O1CCCC1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([O:1][CH2:2][CH2:3][N:4]([CH:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[C:5]([C:7]2[N:8]=[CH:9][N:10]([CH3:12])[CH:11]=2)=[O:6])=[CH:22][CH:21]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: Cn1cnc(C(=O)N(CCO)C2CCOCC2)c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: Cn1cnc(C(=O)N(CCOc2ccc(Cl)cc2)C2CCOCC2)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 47.8 %

Procedure:
To a mixture of N-(2-hydroxyethyl)-1-methyl-N-(tetrahydro-2H-pyran-4-yl)-1H-imidazole-4-carboxamide (150 mg), p-chlorophenol (114 mg), triphenylphosphine (217 mg) and tetrahydrofuran (3.8 mL), DIAD (172 μL) was added under cooling with ice and the resulting mixture was stirred at room temperature for 3 days. To the reaction mixture, water was added and extraction was conducted with diethyl ether. The diethyl ether layer was dried over anhydrous sodium sulfate. After filtering off the desiccant, the solvents were distilled off under reduced pressure and the resulting residue was purified by column chromatography (silica gel cartridge; chloroform/methanol=99:1 and NH silica gel cartridge; hexane/ethyl acetate=1:3 to 1:9) to give the titled compound (103 mg).
Reaction SMILES: [Si]([O:8][C@H:9]1[CH2:18][C@H:17]([O:19][C:20](=[O:33])[C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)([CH3:23])[CH3:22])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:51])[C@@H:15]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([O:43][Si](C(C)(C)C)(C)C)[CH2:37]2)=[CH:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:8][C@H:9]1[CH2:18][C@H:17]([O:19][C:20](=[O:33])[C:21]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)([CH3:22])[CH3:23])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:51])[C@@H:15]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([OH:43])[CH2:37]2)=[CH:10]1
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](OC(=O)C(C)(C)OCc3ccc(F)cc3)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@H]1C=CC2=C[C@@H](O)C[C@H](OC(=O)C(C)(C)OCc3ccc(F)cc3)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O)CC(=O)O1
Yield: 93.3 %

Procedure:
A procedure similar to that described in Example 2, above, was followed, but using 1.03 g of (4R,6R)-6-([1S,2S,6S,8S,8aR]-2-{1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-[2-(4-fluorobenzyloxy)-2-methylpropionyloxy]-2-methyl-1-naphthyl}ethyl)tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example 166 , above] and 19.4 ml of a 1.0 molar solution of tetrabutylammonium fluoride in tetrahydrofuran, to give 666 mg of the title compound as a colorless foam.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[C:17]([F:26])[CH:16]=3)[CH2:12][N:11]([C:27]([N:29]3[CH2:34][CH2:33][S:32][CH2:31][CH2:30]3)=[O:28])[CH2:10]2)[O:6][N:5]=1)[CH3:2].ClC1C=CC=C(C(OO)=[O:43])C=1>>[CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:24])([F:25])[F:23])=[C:17]([F:26])[CH:16]=3)[CH2:12][N:11]([C:27]([N:29]3[CH2:34][CH2:33][S:32](=[O:43])[CH2:31][CH2:30]3)=[O:28])[CH2:10]2)[O:6][N:5]=1)[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOc1noc(C2CC(c3ccc(CC(F)(F)F)c(F)c3)CN(C(=O)N3CCSCC3)C2)n1
Product: CCOc1noc(C2CC(c3ccc(CC(F)(F)F)c(F)c3)CN(C(=O)N3CCS(=O)CC3)C2)n1

Procedure:
76.0 mg (0.151 mmol) of the compound from Example 77 were reacted according to General Method 2 with 47.0 mg (0.136 mmol) of meta-chloroperbenzoic acid. Yield: 60.5 mg (77% of theory)
Reaction SMILES: [CH:1]([O:4][C:5]([C:7]1[CH:8]([CH3:21])[CH2:9][N:10]2[C:14]([CH2:15][C:16](OCC)=[O:17])=[CH:13][S:12][C:11]=12)=[O:6])([CH3:3])[CH3:2].[CH3:22][NH2:23]>>[CH3:22][NH:23][C:16](=[O:17])[CH2:15][C:14]1[N:10]2[CH2:9][CH:8]([CH3:21])[C:7]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])=[C:11]2[S:12][CH:13]=1
Reactant: CCOC(=O)CC1=CSC2=C(C(=O)OC(C)C)C(C)CN12
Reactant: CN
Product: CNC(=O)CC1=CSC2=C(C(=O)OC(C)C)C(C)CN12
Temperature: 20 °C
Reaction time: 24 h

Procedure:
3.3 g of ethyl (7-isopropoxycarbonyl-6-methyl-5,6-dihydropyrrolo[2,1-b]thiazol-3-yl)acetate was added to 60 ml of a 40% aqueous solution of monomethylamine and stirred at 20° C. for 24 hours. The precipitate was collected by filtration, washed with water, dried, and recrystallized from ethanol. Thus 2.2 g of the title compound was obtained.