Diisopropylethylamine → tert-butyl 4-(1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423101Notes

Reaction equation

HRID 423101 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]([OH:50])=O)[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].[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]([NH2:84])[CH2:59][C:60]2[N:61]([C:65]([C:78]3[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=3)([C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)[CH:62]=[CH:63][N:64]=2)=[CH:54][CH:53]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]([NH:84][C:48]([C:33]2([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:26])([CH3:28])[CH3:27])[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:50])[CH2:59][C:60]2[N:61]([C:65]([C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=3)([C:72]3[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=3)[C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)[CH:62]=[CH:63][N:64]=2)=[CH:54][CH:53]=1

Participants

6

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 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2×HCID 577504101-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethanamine2×

Product 1

HCID 57750358tert-butyl 4-(1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (166 mg, 0.44 mmol) was added portionwise to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (150 mg, 0.42 mmol), 1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethanamine (Intermediate 88) (193 mg, 0.42 mmol) and N-ethyldiisopropylamine (0.087 mL, 0.50 mmol) in DMF (2.0 mL) at room temperature. The resulting solution was stirred at room temperature for 3 hours then quenched in water (10 mL) to give a pale yellow ppt. The precipitate was collected by filtration, washed with water and dried under vacuum to afford tert-butyl 4-(1-(4-chlorophenyl)-2-(1-trityl-1H-imidazol-2-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (320 mg, 95%) as a cream solid, which was used without further purification.

Workup

  1. customthen quenched in water (10 mL)
  2. customto give a pale yellow ppt
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water
  5. customdried under vacuum

Sources & evidence

ORD record
ord-8481fdfd0d5442678e7af84d58ee0bff
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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