Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[C:5]2=[N:6][CH:7]=1.[Li][C:19](C)(C)C.CCCCC.CI>CCOCC>[C:14]([Si:11]([CH3:13])([CH3:12])[N:8]1[C:5]2=[N:6][CH:7]=[C:2]([CH3:19])[CH:3]=[C:4]2[CH2:10][CH2:9]1)([CH3:17])([CH3:16])[CH3:15]
Reactant: [Li]C(C)(C)C
Reactant: CC(C)(C)[Si](C)(C)N1CCc2cc(Br)cnc21
Solvent: CCCCC
Solvent: CI
Solvent: CCOCC
Product: Cc1cnc2c(c1)CCN2[Si](C)(C)C(C)(C)C
Temperature: 25 °C

Procedure:
To a stirred and cooled (−78° C.) solution of bromide 4 (0.20 g, 0.64 mmol) in Et2O (2.5 mL) was added dropwise a 1.5 M solution of tert-BuLi in pentane (0.89 mL, 1.34 mmol). After 38 min MeI (0.1 mL, 1.61 mmol) was added dropwise and the mixture allowed to gradually warm to r.t. After 12 h the mixture was partitioned between CHCl3 and saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CHCl3 (2×). The combined organic extracts were dried (MgSO4), and concentrated to afford 7 as a yellow oily residue, which was used directly in the next step without purification.
Reaction SMILES: Cl.[C:2](Cl)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=1.[CH3:11][C:12]([CH3:24])([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([CH3:23])([CH3:22])[CH2:20][OH:21])[CH2:13][OH:14]>N1C=CC=CC=1>[C:2]([O:21][CH2:20][C:19]([CH3:23])([CH3:22])[CH2:18][CH2:17][CH2:16][CH2:15][C:12]([CH3:24])([CH3:11])[CH2:13][O:14][C:2](=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=1)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=1
Reactant: O=C(Cl)c1cccnc1
Reactant: CC(C)(CO)CCCCC(C)(C)CO
Agent: Cl
Solvent: c1ccncc1
Product: CC(C)(CCCCC(C)(C)COC(=O)c1cccnc1)COC(=O)c1cccnc1
Reaction time: 36 h
Yield: 53.3 %

Procedure:
A suspension of 106.2 grams (0.6 mole) of nicotinoyl chloride hydrochloride in 300 ml of anhydrous pyridine was added in 2 hours under stirring with a solution of 20.2 grams (0.1 mole) of 2,2,7,7-tetramethyl-1,8-octanediol in 60 ml of anhydrous pyridine while keeping the temperature at about 70° C. The reaction was refluxed and stirred for 36 hours, then, after cooling, the formed precipitate was removed by filtration. The filtrate was evaporated under vacuum and the obtained residue was treated with a mixture of 200 ml of diethyl ether and 100 ml of an 8% aqueous solution of sodium bicarbonate. The organic layer was separated, washed first with 100 ml of a 3% aqueous solution of sodium bicarbonate, then with 100 ml of water and finally concentrated under vacuum to about half of the initial volume. After standing overnight, the product which separated was recovered by filtration and recrystallized from ethanol thus obtaining 22 grams of the title product, having m.p. 89° -90° C. Yield 53.4% of theoretical.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1.Br[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][OH:27])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CO.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>[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][OH:27])=[CH:21][CH:20]=2)=[CH:11][CH:10]=1
Reactant: C[C@@H]1CCCN1CCc1ccc(B(O)O)cc1
Reactant: OCCc1ccc(Br)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: CO
Solvent: Cc1ccccc1
Product: C[C@@H]1CCCN1CCc1ccc(-c2ccc(CCO)cc2)cc1
Temperature: 100 °C

Procedure:
A mixture of (R)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)phenylboronic acid (1.00 g, 4.29 mmol), 2-(4-bromophenyl)ethanol (0.862 g, 4.29 mmol), 2M Na2CO3 (2.145 mL, 4.29 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.149 g, 0.129 mmol) in toluene (3 mL) and MeOH (0.857 mL) was heated at 100° C. under microwave irradiation for 2.5 h. The mixture was extracted with EtOAc, toluene and DCM. The combined organics were concentrated. The residue was purified by column chromatography and recrystallized from EtOAc to give the title compound. LCMS m/z=310.5 [M+H]+.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:4]([O:5][CH3:6])[CH:3]=1.[NH:13]1[CH2:19][C:17](=[O:18])[NH:16][C:14]1=[O:15].C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:6][O:5][C:4]1[CH:3]=[C:2]([CH:11]=[CH:10][C:7]=1[O:8][CH3:9])[CH:1]=[C:19]1[NH:13][C:14](=[O:15])[NH:16][C:17]1=[O:18]
Reactant: O=C1CNC(=O)N1
Reactant: COc1ccc(C=O)cc1OC
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: COc1ccc(C=C2NC(=O)NC2=O)cc1OC
Reaction time: 2 h
Yield: 38 %

Procedure:
A magnetically stirred mixture of veratraldehyde (9.00 g., 93% pure), hydantoin (5.00 g.), fused, anhydrous sodium acetate (10 g.) and glacial acetic acid (20 ml) was refluxed (bath temperature 160°-165° ) for 1.5 hours (solution within 5 minutes, crystallization during heating period). On cooling, water was added. The mixture was stirred for 1 hour, refrigerated 2 hours, filtered, washed with water and dried overnight at 55°/10 mm. The title compound was obtained as a yellow solid: 4.72 g. (38% yield) m.p. 280°-282°.
Reaction SMILES: [Br:1][C:2]1[CH2:6][C:5]([C:12](OCC)=[O:13])([C:7](OCC)=[O:8])[CH2:4][C:3]=1[Br:17].[H-].C([Al+]CC(C)C)C(C)C.CC(C)=O.[OH-].[Na+]>C1COCC1.O>[Br:1][C:2]1[CH2:6][C:5]([CH2:7][OH:8])([CH2:12][OH:13])[CH2:4][C:3]=1[Br:17]
Reactant: CCOC(=O)C1(C(=O)OCC)CC(Br)=C(Br)C1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(C)=O
Solvent: O
Product: OCC1(CO)CC(Br)=C(Br)C1
Temperature: 25 °C
Yield: 84.8 %

Procedure:
Under nitrogen, a stirred solution of 8.7 g (23.5 mmol) of 1,2-dibromo-4,4-di(carboethoxy)cyclopentene (Step 4) in 70 mL of anhydrous THF at -78° C. was treated with 80 mL of diisobutylaluminum hydride (1.5M in toluene) over a 20 minute period. The reaction was allowed to warm to ambient temperature overnight and was slowly treated with 20 mL of acetone followed by 10 mL of 2.5N sodium hydroxide. Water (100 mL) was added and the solution extracted 5 times with ethyl acetate. The combined extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo to give 5.7 g (85%) of 1,2-dibromo-4,4-di(hydroxymethyl)cyclopentene (10 in Synthetic Scheme III) as a colorless oil: NMR (CDCl3) δ2.20 (s, 2H), 2.50 (s, 4H), 3.70 (s, 4H).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[CH2:4][OH:5].C(N(CC)CC)C.[C:20](Cl)(=[O:22])[CH3:21].C(Cl)(=[O:26])C.C1(C)C=CC=CC=1>C1(C)C=CC=CC=1.CCOCC.O>[C:20]([O:5][C:4](=[O:26])[C:3]1[CH:6]=[C:7]([N+:10]([O-:12])=[O:11])[CH:8]=[CH:9][C:2]=1[Cl:1])(=[O:22])[CH3:21]
Reactant: CC(=O)Cl
Reactant: O=[N+]([O-])c1ccc(Cl)c(CO)c1
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCOCC
Product: CC(=O)OC(=O)c1cc([N+](=O)[O-])ccc1Cl
Temperature: 20 °C
Reaction time: 8 h

Procedure:
27 g of the 2-chloro-5-nitrobenzyl alcohol prepared above in Step 1, was dissolved in 122 ml of toluene. 22 ml of triethylamine was then added. The resultant reaction mixture was cooled to 20° C. and then a solution of 10.2 ml of acetyl chloride in 10 ml of toluene, was added dropwise, keeping the temperature below 20° C. The reaction mixture was then stirred overnight. 2.1 ml of triethylamine and 1.1 ml of acetyl chloride/toluene solution were then added and the reaction mixture was stirred for one hour. 100 ml of water was then added, followed by 50 ml of ether. The resulting organic phase was separated, washed with 2N HCl, aqueous sodium bicarbonate solution and water. The washed organic phase was then dried over magnesium sulfate and the solvent was evaporated, to produce 29.6 g of 2-chloro-5-nitrobenzoyl acetate as a white solid.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([N+:23]([O-:25])=[O:24])=[C:17]([C:19](=[O:22])[CH:20]=[CH2:21])[CH:18]=1)(C(C)(C)C)(C)C.C1COCC1>C(O)(=O)C>[OH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([N+:23]([O-:25])=[O:24])=[C:17]([C:19](=[O:22])[CH:20]=[CH2:21])[CH:18]=1
Reactant: C=CC(=O)c1cc(OCCCO[Si](C)(C)C(C)(C)C)ccc1[N+](=O)[O-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: C=CC(=O)c1cc(OCCCO)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
1-(5'-[3"-(t-Butyidimethylsilyloxy)propyloxy]-2'-nitrophenyl]-2-propen-1-one (the compound of Example 31-(2)) (1.84 g) is mixed with THF (20 ml) and 50% aqueous acetic acid solution (30 ml), and the mixture is stirred at room temperature overnight. The reaction solution is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to give 1-[5'-(3"-hydroxypropyloxy)-2'-nitrophenyl]-2-propen-1-one (1.26 g).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][CH:20]([CH2:23][O:24][C:25]3[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:26]=3[CH:32]([CH3:34])[CH3:33])[CH2:19][CH2:18]2)[N:8]=1)=[O:6].Cl[C:36]1[N:41]=[C:40]([C:42]([NH2:44])=[O:43])[CH:39]=[CH:38][N:37]=1.[K]>C(#N)C>[NH2:44][C:42]([C:40]1[CH:39]=[CH:38][N:37]=[C:36]([NH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][CH:20]([CH2:23][O:24][C:25]4[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:26]=4[CH:32]([CH3:34])[CH3:33])[CH2:19][CH2:18]3)[N:8]=2)=[O:6])[N:41]=1)=[O:43]
Reactant: NC(=O)c1ccnc(Cl)n1
Reactant: Cc1ccc(C(C)C)c(OCC2CCN(CCCNc3nccc(C(=O)NCCN)n3)CC2)c1
Agent: [K]
Solvent: CC#N
Product: Cc1ccc(C(C)C)c(OCC2CCN(CCCNc3nccc(C(=O)NCCNc4nccc(C(N)=O)n4)n3)CC2)c1

Procedure:
2.31 g (4.92 mmol) of N-(2-aminoethyl)-2-[[3-[4-[[5-methyl-2-(1-methylethyl)phenoxy]methyl]piperidin-1-yl]propyl]amino]pyrimidine-4-carboxamide, 0.82 g (5.2 mmol) of 2-chloropyrimidine-4-carboxamide, 0.89 g (6.4 mmol) of potassium carbonateand 75 ml of acetonitrile are introduced, under an argon atmosphere, into a0.25 l round-bottomed flask and the mixture is heated at reflux for 30 h.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:8].C(N(CC)CC)C.[C:32](Cl)(=[O:34])[CH3:33]>C(Cl)Cl>[C:32]([N:13]1[CH2:14][CH2:15][CH:10]([NH:9][C:7](=[O:8])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[O:4][C:3]2[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:2]=2[Cl:1])[CH2:11][CH2:12]1)(=[O:34])[CH3:33]
Reactant: CC(=O)Cl
Reactant: O=C(NC1CCNCC1)c1ccccc1Oc1ccc(Cl)cc1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N1CCC(NC(=O)c2ccccc2Oc2ccc(Cl)cc2Cl)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 75.3 %

Procedure:
To an ice cooled solution of 4-[2-(2,4-dichlorophenoxy)-N-piperidin-4-ylbenzamide (AMR01077, 100 mg, 0.274 mmol) in dry DCM (5 mL) were added triethylamine (0.2 mL, 1.37 mmol) and acetyl chloride (0.023 mL, 0.33 mmol). The reaction mixture was stirred at room temperature until completion by TLC (1.5 h), and quenched with saturated NaHCO3. The organic solution was evaporated to dryness and the oil obtained was purified by column chromatography using DCM/MeOH 95:5 as eluent. Further purification was carried out by treating a DCM solution of the obtained compound with trisamine scavenger (100 mg) for 2 h. The scavenger was filtered off, and the solvent evaporated to give N-(1-acetylpiperidin-4-yl)-2-(2,4-dichlorophenoxy)benzamide (84 mg, 75%) as an oil. Rf: 0.15 (EtOAc) LC/MS (APCI) tr=3.78 min, m/z 409.31 (67), 407.36 (M++H, 100). HPLC tr=2.69 min (96.74%) 1H NMR (270 MHz, CDCl3) δ 1.38 (2H, m, CH2), 2.00 (2H, m, CH2), 2.08 (3H, s, CH3), 2.84 (1H, m, ½CH2), 3.74 (1H, m, ½CH2), 4.18 (1H, m, CH), 4.41 (1H, m, ½CH2), 6.79 (1H, dd, J=8.2, 1.0 Hz, ArH), 6.88 (1H, d, J=8.6 Hz, ArH), 7.22 (1H, dd, J=8.9, 2.5 Hz, ArH), 7.26 (1H, m, ArH), 7.37 (1H, br s, NH), 7.41 (1H, m, ArH), 7.51 (1H, d, J=2.5 Hz, ArH) and 8.17 (1H, dd, J=7.9, 1.7 Hz, ArH).
Reaction SMILES: [N:1](=[C:3]1[N:7]=[C:6]([CH2:8][CH2:9][CH3:10])[C:5]([CH3:12])([CH3:11])[S:4]1)[OH:2].[CH3:13][N:14]=[C:15]=[O:16]>>[CH3:13][NH:14][C:15]([O:2][N:1]=[C:3]1[N:7]=[C:6]([CH2:8][CH2:9][CH3:10])[C:5]([CH3:11])([CH3:12])[S:4]1)=[O:16]
Reactant: CN=C=O
Reactant: CCCC1=NC(=NO)SC1(C)C
Product: CCCC1=NC(=NOC(=O)NC)SC1(C)C

Procedure:
2-oxo-4-propyl-5,5-dimethyl-3-thiazoline-oxime was reacted with methyl isocyanate as described in Example 4 to yield 2-oxo-4-propyl-5,5-dimethyl-3-thiazoline-O-(methylcarbamoyl)-oxime, m.p. 112°-114° C. The 2-oxo-4-propyl-5,5-dimethyl-3-thiazoline-oxime starting material melts at 145°-147° C.
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6](/[C:12](/[C:20]2[NH:25][C:24](=[O:26])[C:23]([CH:27]3[CH2:29][CH2:28]3)=[CH:22][CH:21]=2)=[CH:13]\[C@H:14]2[CH2:18][CH2:17][C:16](=[O:19])[CH2:15]2)[CH:7]=[CH:8][C:9]=1[S:10][CH3:11].Cl>C(O)C.O1CCCC1>[Cl:3][C:4]1[CH:5]=[C:6](/[C:12](/[C:20]2[NH:25][C:24](=[O:26])[C:23]([CH:27]3[CH2:29][CH2:28]3)=[CH:22][CH:21]=2)=[CH:13]\[C@H:14]2[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15]2)[CH:7]=[CH:8][C:9]=1[S:10][CH3:11]
Reactant: CSc1ccc(/C(=C\[C@H]2CCC(=O)C2)c2ccc(C3CC3)c(=O)[nH]2)cc1Cl
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CSc1ccc(/C(=C\[C@H]2CCC(O)C2)c2ccc(C3CC3)c(=O)[nH]2)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.6 %

Procedure:
Sodium borohydride (11 mg) was added to a suspension of 6-{(E)-1-[3-chloro-4-(methylsulfanyl)phenyl]-2-[(1S)-3-oxocyclopentyl]ethenyl}-3-cyclopropylpyridin-2(1H)-one obtained in Example 1-71 (50 mg) in ethanol-tetrahydrofuran (2.5 mL, 4:1) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was poured into 0.5 M hydrochloric acid, followed by extraction with chloroform. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=10:0→9:1) to give the title compound (35 mg, 60%) as a colorless amorphous.
Reaction SMILES: [Br:1][C:2]1[C:22]([F:23])=[CH:21][C:5]2[O:6][C:7]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:8]=3[C@H:9]3[C@H:14]([NH2:15])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[CH3:24][C:25]1([CH3:39])[C@@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:30][P:28]([OH:38])(=[O:29])[O:27][CH2:26]1>C(Cl)Cl.CC(O)C.C(O)C>[OH:38][P:28]1(=[O:29])[O:30][C@@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:25]([CH3:24])([CH3:39])[CH2:26][O:27]1.[Br:1][C:2]1[C:22]([F:23])=[CH:21][C:5]2[O:6][C:7]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:8]=3[C@H:9]3[C@H:14]([NH2:15])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1
Reactant: CC1(C)COP(=O)(O)O[C@@H]1c1ccccc1
Agent: N[C@@H]1CCCN2c3cc(Br)c(F)cc3Oc3cc(F)ccc3[C@@H]12
Solvent: CCO
Solvent: CC(C)O
Solvent: ClCCl
Product: CC1(C)COP(=O)(O)O[C@H]1c1ccccc1
Temperature: 40 °C

Procedure:
To a solution of (±)-(cis)-7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (12.06 g, 31.65 mmol) in 120 mL of CH2Cl2, 25 mL of 2-propanol and 25 mL of ethanol at 40° C. was added a warm solution of (+)-phencyphos (3.84 g, 15.82 mmol) in 50 mL of CH2Cl2, 25 mL of 2-propanol and 25 mL of ethanol. The mixture was heated at 40° C., CH2Cl2 was carefully evaporated until a small amount of crystals was formed, and then the mixture was gradually cooled down to ambient temperature. The precipitate was filtered off and recrystallized to yield the title compound (3.94 g, 20%).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:13]#[C:14][Si](C)(C)C)[CH:8]=2)[O:3]1.C([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O>[CH3:1][C:2]1([CH3:19])[CH2:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:13]#[CH:14])[CH:8]=2)[O:3]1
Reactant: CC1(C)CC(=O)c2cc(C#C[Si](C)(C)C)ccc2O1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CO
Product: C#Cc1ccc2c(c1)C(=O)CC(C)(C)O2
Temperature: 25 °C
Reaction time: 24 h
Yield: 91 %

Procedure:
To a solution of 2,2-dimethyl-6-trimethylsilanylethynyl-chroman-4-one (Compound 261, 4.05 g, 14.87 mmol) in 60.0 mL of MeOH was added K2CO3 (410.9 mg, 2.97 mmol) The resulting mixture was stirred at room temperature for 24 hours, diluted with EtOAc (100 mL) and washed with H2O and saturated aqueous NaCl, and dried over Na2SO4. Concentration of this solution under reduced pressure afforded 2.71 g (91%) of the product as a tan solid. 1H NMR (300 MHz, CDCl3) δ: 8.01 (1H, d, J=2.2 Hz), 7.56 (1H, dd, J=2.2, 8.6 Hz), 6.90 (1H, d, J=8.6 Hz), 3.02 (1H, s), 2.74 (2H, s), 1.47 (6H, s).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@:26]2([CH3:27])[C:9](=[CH:10][CH:11]=[C:12]3[C@@H:25]2[CH2:24][CH2:23][C@@:22]2([CH3:28])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[CH:17]([C:19]([OH:21])=[O:20])[CH3:18])[CH2:8][C@@H:7]([O:29][C:30](=[O:32])[CH3:31])[CH2:6]1)(=[O:3])[CH3:2].[CH3:33]OC(O[C@@H]1[C@@]2(C)C(=CC=C3[C@@H]2CC[C@@]2(C)[C@H]3CC[C@@H]2C(C(O)=O)C)C[C@@H](OC(OC)=O)C1)=O>>[C:1]([O:4][C@@H:5]1[C@@:26]2([CH3:27])[C:9](=[CH:10][CH:11]=[C:12]3[C@@H:25]2[CH2:24][CH2:23][C@@:22]2([CH3:28])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[CH:17]([C:19]([O:21][CH3:33])=[O:20])[CH3:18])[CH2:8][C@@H:7]([O:29][C:30](=[O:32])[CH3:31])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)C(=O)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Reactant: CC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)C(=O)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Product: COC(=O)C(C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C
Yield: 100.3 %

Procedure:
The procedure of Example 7 was repeated except that 89 mg of 1α,3β-diacetoxypregna-5,7-diene-20-carboxylic acid obtained in Example 22 was used in lieu of 85 mg of 1α,3β-bis(methoxycarbonyloxy)pregna-5,7-diene-20-carboxylic acid to give 82 mg of methyl 1α,3β-di-acetoxypregna-5,7-diene-20-carboxylate.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][C@H:9]([CH3:22])[C:8]1=[CH:7][C:6](=[O:23])[CH2:5][CH2:4]2.O[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@]1(CO)C(=CC(=O)CC1)C[C@H]3C>>[CH3:22][C@@H:9]1[C:8]2[C@:3]([CH2:2][OH:1])([CH2:4][CH2:5][C@@H:6]([OH:23])[CH:7]=2)[C@@H:20]2[C@H:11]([C@H:12]3[C@@:16]([CH2:18][CH2:19]2)([CH3:17])[C@@H:15]([OH:21])[CH2:14][CH2:13]3)[CH2:10]1
Reactant: C[C@H]1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(CO)CCC(=O)C=C12
Agent: C[C@@H]1CC2=CC(=O)CC[C@]2(CO)[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Product: C[C@H]1C[C@@H]2[C@H](CC[C@]3(C)[C@@H](O)CC[C@@H]23)[C@@]2(CO)CC[C@@H](O)C=C12

Procedure:
Substituting 17β,19-dihydroxy-4,17α-dimethyl-4-androsten-3-one and 19-hydroxy-6α-methyl-4-androstene-3,17-dione for 17β,19-dihydroxy-7α-methyl-4-androsten-3-one above results in the preparation of 4,17α-dimethyl-4-androstene-3α,17β,19-triol and 6α-methyl-4-androstene-3α,17β,19-triol, respectively.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C@@H:21]3[O:30][C:25]4=[N:26][CH:27]=[CH:28][CH:29]=[C:24]4[O:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[N:11]1([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C@@H:21]3[O:30][C:25]4=[N:26][CH:27]=[CH:28][CH:29]=[C:24]4[O:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc([C@H]3COc4cccnc4O3)cc2)CC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: c1cnc2c(c1)OC[C@H](c1ccc(CN3CCNCC3)cc1)O2
Reaction time: 8 h

Procedure:
To a solution of 4-[(S)-4-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester (prepared from Intermediate C and piperazine-1-carboxylic acid tert-butyl ester according to General Method N) (7.32 g, 17.8 mmol) in 1,4-dioxane (200 mL) is added 4M HCl in 1,4-dioxane (22.2 mL, 88.9 mmol). The resulting slurry is stirred overnight. The reaction is poured into water (600 mL) and basified with 2M aqueous Na2CO3. The product is extracted with DCM, and the combined extracts washed with brine and dried over Na2SO4 to afford the title compound (S) as an oil that partially crystallizes.
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[C:6]([O:10][C:11](=[O:26])[NH:12][C:13]([CH3:25])([CH3:24])[CH2:14][NH:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[Cl:23])([CH3:9])([CH3:8])[CH3:7].C(=O)(O)[O-].[Na+]>CN(C)C(=O)C>[C:6]([O:10][C:11](=[O:26])[NH:12][C:13]([CH3:25])([CH3:24])[CH2:14][N:15]([C:3](=[O:4])[CH2:2][Br:1])[C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[Cl:23])([CH3:9])([CH3:7])[CH3:8]
Reactant: CC(C)(CNc1cc(F)ccc1Cl)NC(=O)OC(C)(C)C
Reactant: O=C(Br)CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(C)(CN(C(=O)CBr)c1cc(F)ccc1Cl)NC(=O)OC(C)(C)C
Reaction time: 0.25 h
Yield: 78.9 %

Procedure:
2.2 ml of bromoacetyl bromide (25.2 mmol) was added to a solution of 5.3 g of [2-(2-chloro-5-fluorophenylamino)-1,1-dimethylethyl]carbamic acid t-butyl ester obtained in Example (62a) (16.8 mmol) in N,N-dimethylacetamide (170 ml) under ice-cooling, and the mixture was stirred at the same temperature for 15 minutes. A saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. Hexane was added to the residue, and the solid was collected by filtration to obtain 5.8 g of the title compound (yield: 80%).
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:14](O)=[O:15])[CH:8]=2)[O:3]1>C1COCC1>[CH3:1][C:2]1([CH3:17])[CH2:11][C:10]([CH3:12])([CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:14][OH:15])[CH:8]=2)[O:3]1
Reactant: CC1(C)CC(C)(C)c2cc(C(=O)O)ccc2O1
Solvent: C1CCOC1
Product: CC1(C)CC(C)(C)c2cc(CO)ccc2O1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of 2,2,4,4-tetramethylchroman 6-carboxylic acid (0.28 g, 1.2 mmol) in THF (5 ml) under N2 was added 1M of LiALH4 /THF (1.15 ml, 1.15 mmol). The reaction mixture was left at room temperature for overnight, followed by addition of ice-water to the reaction. The reaction mixture was extracted with ethyl acetate, the organic extracts were dried and concentrated to give 2,2,4,4-tetramethyl-chroman-6-yl methanol as a white solid. Without further purification, the alcohol was dissolved in CH2Cl2 (5 ml) and MnO2 (1.04 g, 12 mmol) was added. The resulting mixture was stirred at room temperature for 5 hours. After filtration, the resulting colorless clear solution was concentrated and purified by column chromatography (silica gel, 10% ethyl acetate in hexane) to give the title compound as a colorless oil (0.147 g, 57%). 1H NMR d 1.39 (d, 12H), 1.88 (s, 2H), 6.89 (d, J=8.4 Hz, 1H), 7.62 (dd, J1 =2.0 Hz, J2 =8.4 Hz, 1H), 7.85 (d, J=2.0 Hz, 1H), 9.86 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1>CO.[Pd]>[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1
Reactant: Cc1ccc2cccnc2c1
Agent: [Pd]
Solvent: CO
Product: Cc1ccc2c(c1)NCCC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.7 %

Procedure:
To a solution of 7-methylquinoline (2.00 g) in methanol (40 ml), 10% palladium on activated carbon (200 mg) was added and stirred overnight under a hydrogen atmosphere (60 psi) at room temperature. After the reaction mixture was filtered through celite, the solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=20:1 to 10:1) to give the titled compound, i.e., 7-methyl-1,2,3,4-tetrahydroquinoline (2.05 g) as a yellow oil.