Hydrochloric Acid → HCID 86695222, compound

HRID 1504061Notes

Reaction equation

HRID 1504061 reaction equation
[C:1]([C@@H:4]([NH:28]C(=O)OCC1C=CC=CC=1)[CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([N:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]4)[C:8]=3[C:7]1=2)(=[O:3])[NH2:2].Cl>ClCCl>[NH2:28][C@@H:4]([CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:20][CH2:21][CH:22]([N:25]([CH3:26])[CH3:27])[CH2:23][CH2:24]4)[C:8]=3[C:7]1=2)[C:1]([NH2:2])=[O:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695219HCID 86695219, compound

Product 1

HCID 86695222HCID 86695222, compoundYield 39.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of benzyl N-[(1S)-1-carbamoyl-2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethyl]carbamate (40 mg, 0.07 mmol, 1.00 equiv) in dichloromethane (2 mL) was added hydrochloric acid (conc., 1 mL) and the resulting solution was stirred for 5 h at 30° C. The resulting mixture was concentrated under vacuum and the crude product was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm; Mobile phase: water with 0.03% NH3.H2O and CH3CN (13.0% CH3CN up to 30.0% in 10 min, up to 100.0% in 2 min, down to 13.0% in 2 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and concentrated to remove CH3CN and water under reduced pressure. The residue was lyophilized overnight to give (2S)-2-amino-3-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide (11.2 mg, 37%) as a white solid. MS: m/z 404 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.40-1.50 (m, 4H), 1.68-1.75 (m, 2H), 2.00-2.10 (m, 2H), 2.12-2.18 (m, 1H), 2.25-2.35 (m, 2H), 2.33 (s, 6H), 2.50-2.60 (m, 1H), 2.65-2.75 (m, 1H), 2.90-2.95 (m, 1H), 3.00-3.15 (m, 1H), 3.35-3.48 (m, 2H), 5.20-5.30 (m, 1H), 8.42 (s, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customthe crude product was purified by preparative HPLC under the following conditions (Waters)
  3. waitMobile phase: water with 0.03% NH3.H2O and CH3CN (13.0% CH3CN up to 30.0% in 10 min
  4. waitup to 100.0% in 2 min
  5. waitdown to 13.0% 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-46107f685e63466c8bfbf8b21f62ed28
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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