Bromoacetyl bromide → HCID 178424807, compound

HRID 2409794Notes

Reaction equation

HRID 2409794 reaction equation
Br[CH2:2][C:3](Br)=[O:4].[NH2:6][CH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]1.C(N(C(C)C)C(C)C)C.[CH3:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:32]=1[NH:38][C:39]([NH:41]/[N:42]=[CH:43]/[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[N:54]=[CH:53][N:52]([C:55]3[CH:60]=[CH:59][C:58]([O:61][C:62]([F:65])([F:64])[F:63])=[CH:57][CH:56]=3)[N:51]=2)=[CH:46][CH:45]=1)=[S:40]>ClC(Cl)C.ClCCl.C(#N)C>[CH3:37][C:33]1[CH:34]=[CH:35][CH:36]=[C:31]([CH3:30])[C:32]=1/[N:38]=[C:39](/[NH:41]/[N:42]=[CH:43]/[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[N:54]=[CH:53][N:52]([C:55]3[CH:60]=[CH:59][C:58]([O:61][C:62]([F:64])([F:65])[F:63])=[CH:57][CH:56]=3)[N:51]=2)=[CH:46][CH:45]=1)\[S:40][CH2:2][C:3]([NH:6][CH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]1)=[O:4]

Participants

8

Reactant 4

HCID 61147Bromoacetyl bromideHCID 81531DiisopropylethylamineHCID 1502022tert-Butyl (3S)-3-(aminomethyl)piperidine-1-carboxylateHCID 885903131-(2,6-dimethylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thiourea

Product 1

HCID 178424807HCID 178424807, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of bromoacetyl bromide (26 microliters (μL), 0.299 mmol) in dichloroethane (3 mL) was added dropwise a solution of (S)-tert-butyl 3-(aminomethyl)piperidine-1-carboxylate (63.9 mg, 0.298 mmol) in dichloromethane (1 mL), followed by N-ethyl-N-isopropylpropan-2-amine (76 mg, 0.588 mmol). This mixture was stirred at room temperature for 30 min, then (E)-N-(2,6-dimethylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazine-carbothioamide (100 mg, 0.196 mmol) was added as a solid and the mixture was heated to 40° C. for 90 min. It was then allowed to cool to room temperature and evaporated under reduced pressure, giving a light yellow glass, which was dissolved in acetonitrile (2 mL) and allowed to stand at room temperature. The resulting precipitate was isolated by centrifuge and decanting, washing with fresh acetonitrile. The solid was dried under a nitrogen stream and then under high vacuum. The crude product was recrystallized from acetone-isopropyl alcohol. The title compound was isolated as a white solid (36.5 mg, 24%): mp 148-151° C.; 1H NMR (400 MHz, methanol-d4) δ 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J=8.1 Hz, 2H), 8.12 (m, 2H), 8.07-8.00 (m, 2H), 7.58-7.43 (m, 2H), 7.33 (dd, J=8.6, 6.5 Hz, 1H), 7.25 (d, J=7.6 Hz, 2H), 4.02 (m, 2H), 3.97-3.75 (m, 2H), 3.21 (d, J=6.9 Hz, 2H), 2.90 (m, 1H), 2.59 (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78-1.63 (m, 2H), 1.44 (s, 9H), 1.29 (m, 3H); ESIMS m/z 765 (M+H).

Workup

  1. temperaturethe mixture was heated to 40° C. for 90 min
  2. temperatureto cool to room temperature
  3. customevaporated under reduced pressure
  4. customgiving a light yellow glass, which
  5. customto stand at room temperature
  6. customThe resulting precipitate was isolated by centrifuge
  7. customdecanting
  8. washwashing with fresh acetonitrile
  9. customThe solid was dried under a nitrogen stream
  10. customThe crude product was recrystallized from acetone-isopropyl alcohol

Sources & evidence

ORD record
ord-c522d5b9786748748791b4f29dfbdb84
Source dataset
uspto-grants-2014_08
Patent number
US08815922B2

Reaction notes

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