Reaction SMILES: Cl.[CH3:2][NH:3][CH:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[C:22]3[C:21]4[C@@H:20]([CH2:23][C@H:24]([C:26]5[CH:30]=[CH:29][NH:28][N:27]=5)[OH:25])[CH2:19][CH2:18][C:17]=4[S:16][C:15]=3[N:14]=[CH:13][N:12]=2)[CH2:6][CH2:5]1.C=O.[BH3-][C:34]#N.[Na+]>CO>[CH3:2][N:3]([CH3:34])[CH:4]1[CH2:5][CH2:6][CH:7]([O:10][C:11]2[N:12]=[CH:13][N:14]=[C:15]3[C:22]=2[C:21]2[C@@H:20]([CH2:23][C@H:24]([C:26]4[CH:30]=[CH:29][NH:28][N:27]=4)[OH:25])[CH2:19][CH2:18][C:17]=2[S:16]3)[CH2:8][CH2:9]1
Reactant: CNC1CCC(Oc2ncnc3sc4c(c23)[C@@H](C[C@@H](O)c2cc[nH]n2)CC4)CC1
Reactant: [BH3-]C#N
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CN(C)C1CCC(Oc2ncnc3sc4c(c23)[C@@H](C[C@@H](O)c2cc[nH]n2)CC4)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of tert-butyl N-(4-[[(3R)-3-[(2R)-2-hydroxy-2-(1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-3-yl)ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (70 mg, 0.11 mmol, 1.00 equiv) in dichloromethane (10 mL) was added hydrochloric acid (2 M, 1 mL) with stirring at 0° C. The resulting solution was stirred for 24 h at room temperature and concentrated under vacuum to give 60 mg of the crude (1R)-2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]-1-(1H-pyrazol-3-yl)ethan-1-ol hydrochloride as a yellow solid. The crude hydrochloride in 5 mL of methanol was added HCHO (37%, 0.5 mL) and the reaction solution was stirred at room temperature for 30 min. The NaBH3CN (18 mg, 0.30 mmol, 3.10 equiv) was added to the mixture and the resulting solution was stirred for 4 h at ambient temperature. After concentration in vacuo, the crude product was purified by preparative HPLC under the following conditions (Waters): column: X-briage C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 20 mM NH4HCO3 (10.0% CH3CN up to 50.0% in 10 min, up to 95% in 2 min, down to 10.0% in 2 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired (1R)-2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]-1-(1H-pyrazol-3-yl)ethan-1-ol (26 mg) as a white solid. MS (ES): m/z 428 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 8.46 (s, 1H), 7.50 (s, 1H), 6.27 (s, 1H), 5.25-5.29 (m, 1H), 3.67-3.71 (m, 1H), 3.01-3.15 (m, 1H), 2.97-3.00 (m, 1H), 2.57-2.65 (m, 3H), 2.46 (s, 6H), 2.30-2.34 (m, 3H), 2.08-2.10 (m, 2H), 1.90-1.92 (m, 1H), 1.85-1.89 (m, 2H), 1.53-1.59 (m, 2H), 1.30-1.37 (m, 1H). Synthesis of Compound I-96. To a solution of tert-butyl N-(4-[[(3R)-3-[(2S)-2-hydroxy-2-(1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-3-yl)ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (180 mg, 0.28 mmol, 1.00 equiv) in dichloromethane (10 mL) was added hydrochloric acid (12 M, 1 mL) with stirring at 0° C. The resulting solution was stirred for 24 h at room temperature and concentrated under vacuum to give 160 mg of the crude (1S)-2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]-1-(1H-pyrazol-3-yl)ethan-1-ol hydrochloride as a yellow solid. The crude hydrochloride in 5 mL of methanol was added HCHO (37%, 0.5 mL) and the reaction solution was stirred at room temperature for 30 min. The NaBH3CN (46 mg, 0.73 mmol, 3.0 equiv) was added to the mixture and the resulting solution was stirred for 4 h at ambient temperature. After concentration in vacuo, the crude product was purified by preparative HPLC under the following conditions (Waters): column: X-briage C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 20 mM NH4HCO3 (10.0% CH3CN up to 50.0% in 10 min, up to 95% in 2 min, down to 10.0% in 2 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired (1S)-2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]-1-(1H-pyrazol-3-yl)ethan-1-ol (65.9 mg) as a white solid. MS (ES): m/z 428 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 8.45 (s, 1H), 7.65 (s, 1H), 6.35 (s, 1H), 5.23-5.25 (m, 1H), 4.92-4.95 (m, 1H), 3.36-3.38 (m, 1H), 3.10-3.15 (m, 1H), 2.93-2.98 (m, 1H), 2.71-2.74 (m, 1H), 2.51-2.52 (m, 2H), 2.48 (s, 6H), 2.15-2.17 (m, 2H), 1.89-2.03 (m, 3H), 1.44-1.49 (m, 4H).