Diisopropylethylamine → HCID 57750361, compound

HRID 423053Notes

Reaction equation

HRID 423053 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[C:25]([O:29][C:30]([NH:32][C:33]1([C:48](O)=[O:49])[CH2:38][CH2:37][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:35][CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)C(C)C)(C)C.[Cl:60][C:61]1[CH:66]=[CH:65][C:64]([CH:67]([NH2:73])[CH2:68][CH2:69][N:70]([CH3:72])[CH3:71])=[CH:63][CH:62]=1>CN1C(=O)CCC1.CO>[Cl:60][C:61]1[CH:62]=[CH:63][C:64]([CH:67]([NH:73][C:48]([C:33]2([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:27])([CH3:28])[CH3:26])[CH2:38][CH2:37][N:36]([C:39]3[C:40]4[CH:47]=[CH:46][NH:45][C:41]=4[N:42]=[CH:43][N:44]=3)[CH2:35][CH2:34]2)=[O:49])[CH2:68][CH2:69][N:70]([CH3:72])[CH3:71])=[CH:65][CH:66]=1

Participants

7

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 11557554HCID 11557554, compound2×HCID 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2×

Product 1

HCID 57750361HCID 57750361, compoundYield 76.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
50 °C

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.044 g, 0.12 mmol) was added to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.040 g, 0.11 mmol) and N,N-diisopropylethylamine (0.023 mL, 0.13 mmol) in NMP (5 mL) at 22° C. The resulting suspension was stirred at 50° C. for 10 minutes. The mixture was cooled to ambient temperature and 1-(4-chlorophenyl)-N3,N3-dimethylpropane-1,3-diamine (Intermediate 33) (0.023 g, 0.11 mmol) was added as a solution in NMP (2 mL). The mixture was stirred at 22° C. for 3 days. The mixture was diluted with methanol and purified by ion exchange chromatography using an SCX column; the desired product was eluted from the column using 30% (2M NH3 in MeOH) in DCM and product-containing fractions were evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 2 to 6% (10:1 MeOH/conc. NH3 (aq)) in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-(dimethylamino)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (0.047 g, 76%) as a white solid.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. stirringThe mixture was stirred at 22° C. for 3 days
  3. custompurified by ion exchange chromatography
  4. washthe desired product was eluted from the column
  5. additionproduct-containing fractions
  6. customwere evaporated to dryness
  7. customThe crude product was purified by flash silica chromatography, elution gradient 2 to 6% (10:1 MeOH/conc. NH3 (aq)) in DCM
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-cee351e9c2e04bfa9af38af390dddc05
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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