Cyclobutylamine → HCID 25191753, compound

HRID 1878363Notes

Reaction equation

HRID 1878363 reaction equation
[C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)[Cl:4].[NH2:13][C:14]1[CH:41]=[CH:40][C:17]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]3[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=3)[C:30]([NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:22][CH2:21]2)=[O:19])=[C:16]([F:42])[C:15]=1[F:43].C(N(C(C)C)C(C)C)C.[CH:53]1([NH2:57])[CH2:56][CH2:55][CH2:54]1>ClCCl.O>[ClH:4].[C:33]([NH:32][C:30](=[O:31])[C:29]1[CH:37]=[CH:38][CH:39]=[C:27]([CH2:26][N:23]2[CH2:22][CH2:21][N:20]([C:18](=[O:19])[C:17]3[CH:40]=[CH:41][C:14]([NH:13][C:1]([NH:57][CH:53]4[CH2:56][CH2:55][CH2:54]4)=[O:12])=[C:15]([F:43])[C:16]=3[F:42])[CH2:25][CH2:24]2)[CH:28]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 75645CyclobutylamineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 57917583HCID 57917583, compound

Product 1

HCID 25191753HCID 25191753, compoundYield 115.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of bis(trichloromethyl) carbonate (0.26 mmol, 76 mg) in dichloromethane (3 mL) was added a mixture of 3-((4-(4-amino-2,3-difluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide (0.6 mmol, 257 mg) and N-ethyl-N-isopropylpropan-2-amine (0.11 mL) in dichloromethane (2 mL) dropwise over 2 minutes. After 30 minutes stirring, a mixture of cyclobutylamine (1.192 mmol, 0.113 mL, 85 mg) and N-ethyl-N-isopropylpropan-2-amine (0.22 mL) was added. After 2 hours stirring, the reaction mixture was diluted with dichloromethane and water. The organic layer separated, dried with sodium sulfate and purified by basic reverse phase HPLC. The water/acetonitrile fractions were concentrated under vacuum. The residue was taken up in dichloromethane (1 mL) and 2M hydrochloric acid (2 mL) in ether was added. The volatiles were removed under reduced pressure. Drying in a vacuum oven over night at 50° C. gave the title compound (170 mg). MS (ESI) m/z 528.5[M+H]+

Workup

  1. additionwas added
  2. stirringAfter 2 hours stirring
  3. customThe organic layer separated
  4. dry with materialdried with sodium sulfate
  5. custompurified by basic reverse phase HPLC
  6. concentrationThe water/acetonitrile fractions were concentrated under vacuum
  7. addition2M hydrochloric acid (2 mL) in ether was added
  8. customThe volatiles were removed under reduced pressure
  9. customDrying in a vacuum oven over night at 50° C.

Sources & evidence

ORD record
ord-b51553393729430985d62967a154f6ba
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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