Hydrochloric Acid → HCID 86695224, compound

HRID 1504063Notes

Reaction equation

HRID 1504063 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([CH2:7][C@H:8]2[CH2:19][CH2:18][C:17]3[S:16][C:15]4[N:14]=[CH:13][N:12]=[C:11]([O:20][CH:21]5[CH2:26][CH2:25][CH:24]([N:27](C)[C:28](=O)OC(C)(C)C)[CH2:23][CH2:22]5)[C:10]=4[C:9]2=3)[C:4](=[O:36])[NH:3]1.Cl>ClCCl>[CH3:28][NH:27][CH:24]1[CH2:25][CH2:26][CH:21]([O:20][C:11]2[C:10]3[C:9]4[C@@H:8]([CH2:7][C@H:5]5[NH:6][C:2](=[O:1])[NH:3][C:4]5=[O:36])[CH2:19][CH2:18][C:17]=4[S:16][C:15]=3[N:14]=[CH:13][N:12]=2)[CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695223HCID 86695223, compound

Product 1

HCID 86695224HCID 86695224, compoundYield 44.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-(4-[[(3R)-3-[[(4R)-2,5-dioxoimidazolidin-4-yl]methyl]-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 (45 mg, 0.09 mmol, 1.00 equiv) in dichloromethane (3 mL) was added hydrogen chloride (conc., 0.5 mL) at 0° C. under nitrogen. The resulting solution was stirred for 2 h at room temperature and evaporated under reduced pressure. The crude product (45 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Shield RP18 OBD column: 5 um, 19*150 mm; mobile phase: water with 0.03% NH3.H2O and CH3CN (16% CH3CN up to 22% in 11 min, up to 100% in 2 min, down to 16% in 2 min); UV detection at 254 and 220 nm. The product-containing fractions were collected and concentrated to remove CH3CN and water under reduced pressure. The residue was lyophilized overnight to give (5R)-5-[[(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]methyl]imidazolidine-2,4-dione (16.5 mg) as a white solid. MS: m/z 416 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.20-1.40 (m, 2H), 1.50-1.65 (m, 2H), 1.72-1.95 (m, 1H), 2.00-2.37 (m, 6H), 2.45 (s, 3H), 2.56-2.68 (m, 2H), 2.98-3.05 (m, 1H), 3.08-3.15 (m, 1H), 3.50 (t, 1H, J=1.5 Hz), 4.19 (dd, 2H, J=11.7, 2.7 Hz), 5.20-5.30 (m, 1H), 8.42 (s, 1H).

Workup

  1. customevaporated under reduced pressure
  2. customThe crude product (45 mg) was purified by preparative HPLC under the following conditions (Waters)
  3. waitmobile phase: water with 0.03% NH3.H2O and CH3CN (16% CH3CN up to 22% in 11 min
  4. waitup to 100% in 2 min
  5. waitdown to 16% in 2 min)
  6. customThe product-containing fractions were collected
  7. concentrationconcentrated
  8. customto remove CH3CN and water under reduced pressure
  9. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-80f526f83725440d98d5ce8c82748fcc
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…