Diisopropylethylamine → HCID 86604270, compound

HRID 269472Notes

Reaction equation

HRID 269472 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=3[F:31])=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.[C:32]([O:36][N:37]([CH2:41][C:42](O)=[O:43])[C:38]([CH3:40])=[O:39])([CH3:35])([CH3:34])[CH3:33].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(Cl)Cl.CO>[C:32]([O:36][N:37]([CH2:41][C:42]([NH:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]4[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=4[F:31])=[CH:20][CH:21]=3)[CH2:13][CH2:14]2)[CH:4]=1)=[O:43])[C:38]([CH3:40])=[O:39])([CH3:35])([CH3:34])[CH3:33]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22142721HCID 22142721, compoundHCID 69217766HCID 69217766, compound

Product 1

HCID 86604270HCID 86604270, compoundYield 90.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-methyl-3-(1-{[4-(2,4,5-trifluorophenoxy)phenyl]methyl}(4-piperidyl))phenylamine (271 mg, 0.64 mmol) in dimethylformamide (15 mL) was added 2-[(tert-butoxy)-N-methylcarbonylamino]acetic acid (361 mg, 1.91 mmol) followed by O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 728 mg, 1.91 mmol) and diisopropylethylamine (328 mg, 2.54 mmol). After stirring at room temperature for 21 h, the reaction mixture was partitioned between CH2Cl2 (30 mL) and saturated aqueous NaHCO3 (30 mL). The organic layer was washed with water (3×30 mL) and brine (30 mL), dried over MgSO4 and concentrated in vacuo provided the crude product. Purification on silica gel (silica gel 60, 40 mL) eluting with CH2Cl2 then 3% methanol in CH2Cl2 to give 2-[(tert-butoxy)-N-methylcarbonylamino]-N-[4-methyl-3-(1-{[4-(2,4,5-trifluorophenoxy)phenyl]methyl}(4-piperidyl))phenyl]acetamide (345 mg, 0.58 mmol, 90% yield) as a white solid. LCMS (method B): 2.81 min, 598.3 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned between CH2Cl2 (30 mL) and saturated aqueous NaHCO3 (30 mL)
  2. washThe organic layer was washed with water (3×30 mL) and brine (30 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customprovided the crude product
  6. customPurification on silica gel (silica gel 60, 40 mL)
  7. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-83717e3f33be45528c18057a2db56dbf
Source dataset
uspto-grants-2008_11
Patent number
US07446204B2

Reaction notes

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