Diisopropylethylamine → HCID 57750396, compound

HRID 423112Notes

Reaction equation

HRID 423112 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(C(C)C)C(C)C)C.[Cl:60][C:61]1[CH:66]=[CH:65][C:64]([CH:67]([NH2:72])[CH2:68][CH2:69][O:70][CH3:71])=[CH:63][CH:62]=1>CN1C(=O)CCC1.CCOC(C)=O>[Cl:60][C:61]1[CH:62]=[CH:63][C:64]([CH:67]([NH:72][C:48]([C:33]2([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:34][CH2:35][N:36]([C:39]3[C:40]4[CH:47]=[CH:46][NH:45][C:41]=4[N:42]=[CH:43][N:44]=3)[CH2:37][CH2:38]2)=[O:49])[CH2:68][CH2:69][O:70][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 57750328HCID 57750328, compound2×HCID 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2×

Product 1

HCID 57750396HCID 57750396, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
50 °C

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (55.2 mg, 0.15 mmol) was added to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (50 mg, 0.14 mmol) and N-ethyldiisopropylamine (0.029 mL, 0.17 mmol) in NMP (5 mL). The resulting solution was stirred at 50° C. for 10 minutes then cooled to ambient temperature. 1-(4-Chlorophenyl)-3-methoxypropan-1-amine (Intermediate 100) (27.6 mg, 0.14 mmol) was added as a solution in NMP (2 mL). The resulting mixture was stirred at 22° C. for 16 hours. The reaction mixture was diluted with EtOAc (75 mL) and washed sequentially with water (6×75 mL), and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 1 to 4% (10:1 MeOH/conc. NH3 (aq)) in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-methoxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (52.0 mg, 69.2%) as a white solid.

Workup

  1. temperaturethen cooled to ambient temperature
  2. stirringThe resulting mixture was stirred at 22° C. for 16 hours
  3. washwashed sequentially with water (6×75 mL), and saturated brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 1 to 4% (10:1 MeOH/conc. NH3 (aq)) in DCM
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-3a1697bcba4e4401aa6dffab8ac162bc
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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