Diisopropylethylamine → HCID 57750401, compound

HRID 423060Notes

Reaction equation

HRID 423060 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].CCN(C(C)C)C(C)C.[NH2:60][C@@H:61]([C:67]1[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][CH:68]=1)[CH2:62][C:63]([O:65][CH3:66])=[O:64]>CN1C(=O)CCC1.CCOC(C)=O>[C:25]([O:29][C:30]([NH:32][C:33]1([C:48]([NH:60][C@@H:61]([C:67]2[CH:68]=[CH:69][C:70]([Cl:73])=[CH:71][CH:72]=2)[CH2:62][C:63]([O:65][CH3:66])=[O:64])=[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])([CH3:26])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2400965HCID 2400965, compound2×HCID 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×

Product 1

HCID 57750401HCID 57750401, compoundYield 104.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
20 °C

Procedure

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (0.579 g, 1.52 mmol) was added in one portion to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.5 g, 1.38 mmol) and DIPEA (0.503 mL, 3.04 mmol) in NMP (5 mL) at 20° C. The resulting solution was stirred at 20° C. for 5 minutes. (R)-methyl 3-amino-3-(4-chlorophenyl)propanoate (hydrochloride) (Intermediate 40) (0.346 g, 1.38 mmol) was then added to the solution and stirred at room temperature for 3 hours. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with water (50 mL), water (50 mL), and water (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 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford (R)-methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate (0.800 g, 100%) as a white solid.

Workup

  1. stirringstirred at room temperature for 3 hours
  2. washwashed sequentially with water (50 mL), water (50 mL), and water (50 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-29bc1f038d3b4b97aae802c021dc298e
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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