Hydrochloric Acid → HCID 68109783, compound

HRID 1503948Notes

Reaction equation

HRID 1503948 reaction equation
[C:1]([CH:3]([O:33][CH3:34])[CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:23][CH2:22][CH:21]([N:24](C)[C:25](=O)OC(C)(C)C)[CH2:20][CH2:19]4)[C:7]=3[C:6]1=2)#[N:2].Cl>ClCCl>[CH3:34][O:33][C@@H:3]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:19][CH2:20][CH:21]([NH:24][CH3:25])[CH2:22][CH2:23]4)[C:7]=3[C:6]1=2)[C:1]#[N:2].[CH3:34][O:33][C@H:3]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:19][CH2:20][CH:21]([NH:24][CH3:25])[CH2:22][CH2:23]4)[C:7]=3[C:6]1=2)[C:1]#[N:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68110180HCID 68110180, compound

Product 2

HCID 68109783HCID 68109783, compoundHCID 68115403HCID 68115403, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round-bottom flask, a solution of tert-butyl N-(4-[[(3R)-3-(2-cyano-2-methoxyethyl)-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 (100 mg, 0.21 mmol, 1.00 equiv) in dichloromethane (10 mL) was added hydrochloric acid (12 M, 0.5 mL) in a water/ice bath and stirred for 4 h. After completion and concentration in vacuo, the residue was neutralised with saturated aqueous sodium bicarbonate, extracted with 3×50 mL of DCM. The combined organic layers were concentrated under vacuum and the crude product (80 mg) was purified by preparative HPLC under the following conditions: (SHIMADZU): column: Xbridge Prep C18 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 56.0% in 15 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 corresponding (2S)-2-methoxy-3-[(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]propanenitrile (12.5 mg) as a off-white semi-solid and (2R)-2-methoxy-3-[(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]propanenitrile (3.5 mg) as a light yellow semi-solid, respectively.

Workup

  1. concentrationAfter completion and concentration in vacuo
  2. extractionextracted with 3×50 mL of DCM
  3. concentrationThe combined organic layers were concentrated under vacuum
  4. customthe crude product (80 mg) was purified by preparative HPLC under the following conditions
  5. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 56.0% in 15 min)
  6. customThe product-containing fractions were collected
  7. custompartially evaporated
  8. customto remove water and CH3CN under reduced pressure
  9. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-db7653a7c8324f5293215a5df5940ca5
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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