Dichloromethane → HCID 118161075, compound

HRID 928688Notes

Reaction equation

HRID 928688 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:14]=[C:13]([C:15]2[N:16]=[C:17]([N:24]([C:32]3[CH:37]=[CH:36][C:35]([N:38]4[CH2:43][CH2:42][O:41][C@@H](COC(OC(C)(C)C)=O)[CH2:39]4)=[CH:34][CH:33]=3)C(=O)OC(C)(C)C)[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[CH:20]=2)[CH:12]=[N:11][CH:10]=1)=O)(C)(C)C.[C:60]([OH:66])([C:62](F)(F)F)=O.[CH2:67](Cl)Cl>>[NH2:8][C:9]1[N:14]=[C:13]([C:15]2[N:16]=[C:17]([NH:24][C:32]3[CH:37]=[CH:36][C:35]([N:38]4[CH2:43][CH2:42][O:41][C@@H:62]([CH2:60][OH:66])[CH2:39]4)=[CH:34][CH:33]=3)[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[CH:20]=2)[CH:12]=[N:11][C:10]=1[CH3:67]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acid2×HCID 118185273HCID 118185273, compound

Product 1

HCID 118161075HCID 118161075, compound

Procedure

(R)-tert-butyl (6-(6-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)(4-(2-(((tert-butoxycarbonyl)oxy)methyl)morpholino)phenyl)carbamate XX (460 mg, 0.56 mmol) in DCM was added to a round bottom flask, and TFA (1.29 ml, 16.85 mmol) was added. The reaction was partially complete after stirring ˜5 hours. Added an additional 10 eq TFA and stirred overnight, then concentrated under reduced pressure. 10% MeOH/DCM (˜100 mL) and sat.aq. sodium bicarbonate were added and stirred 15 min, separated, extracted with ˜100 mL 10% MeOH/DCM. The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure and dried under vacuum. The resulting solid was triturated with DCM, collected solids via filtration and dried under vacuum to give compound 3. LCMS-ESI+ (m/z): [M+H]+: 419.2. 1H NMR (300 MHz d6-DMSO) δ: 9.57 (s, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 8.13 (d, J=1.2 Hz, 1H), 8.06-7.90 (m, 2H), 7.87 (s, 1H), 7.62 (d, J=1.1 Hz, 1H), 7.05-6.93 (m, 2H), 6.49 (s, 2H), 4.78 (t, J=5.8 Hz, 1H), 3.98-3.87 (m, 1H), 3.71-3.36 (m, 7H), 2.63 (td, J=11.7, 3.4 Hz, 1H), 2.37 (dd, J=12.1, 10.5 Hz, 1H). The corresponding (S) isomer, or racemic mixture of compounds is prepared similarly, using (S)-(4-(4-aminophenyl)morpholin-2-yl)methanol or a racemic mixture of (4-(4-aminophenyl)morpholin-2-yl)methanol, respectively, in the first step.

Workup

  1. stirringstirred overnight
  2. concentrationconcentrated under reduced pressure
  3. additionsodium bicarbonate were added
  4. stirringstirred 15 min
  5. customseparated
  6. extractionextracted with ˜100 mL 10% MeOH/DCM
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customdried under vacuum
  12. customThe resulting solid was triturated with DCM
  13. customcollected solids
  14. filtrationvia filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-7ae541ed5dc34d029809a7882742e024
Source dataset
uspto-grants-2016_03
Patent number
US09290505B2

Reaction notes

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