Isonicotinic Acid → HCID 67988170, compound

HRID 2168202Notes

Reaction equation

HRID 2168202 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:34][C:35]1[C:43]2[C:42]([N:44]3[CH2:49][CH2:48][CH:47]([NH:50][CH3:51])[CH2:46][CH2:45]3)=[N:41][CH:40]=[N:39][C:38]=2[N:37]([S:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)(=[O:54])=[O:53])[CH:36]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C)C=O.[Cl-].[Na+].O.C(Cl)Cl>[Br:34][C:35]1[C:43]2[C:42]([N:44]3[CH2:49][CH2:48][CH:47]([N:50]([CH3:51])[C:7]([C:4]4[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=4)=[O:9])[CH2:46][CH2:45]3)=[N:41][CH:40]=[N:39][C:38]=2[N:37]([S:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)(=[O:54])=[O:53])[CH:36]=1

Participants

9

Reactant 5

HCID 5922Isonicotinic AcidHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67988152HCID 67988152, compound

Product 1

HCID 67988170HCID 67988170, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

4-pyridinecarboxylic acid (30.3 mg, 0.247 mmol) was dissolve in N,N-Dimethylformamide (DMF) (3 mL) under argon flow. HATU (86 mg, 0.226 mmol) was added. After 30 minutes of stirring, 1-[5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-N-methyl-4-piperidinamine D25 (100 mg) was added. After 20 minutes of stirring, DIPEA (0.144 mL, 0.822 mmol) was added. The mixture was stirred at room temperature under argon flow for all the night. DCM (10 mL) has been added to the mixture. The work-up has been done with 2×10 mL of Na2CO3, 10 mL of brine. The organic layer was filtrated by a phase separator and put under vacuo to remove the solvent. The crude material was purified by silica chromatography eluting by a gradiant of solvent: 0-5% of MeOH in DCM. The fractions were collected and the solvent has been evaporated to give the product D26 in 41 mg. LCMS [M+H]+555.01/557.03 g 2.64 min (5 min run)

Workup

  1. stirringAfter 20 minutes of stirring
  2. stirringThe mixture was stirred at room temperature under argon flow for all the night
  3. filtrationThe organic layer was filtrated by a phase separator
  4. customto remove the solvent
  5. customThe crude material was purified by silica chromatography
  6. washeluting by a gradiant of solvent
  7. customThe fractions were collected
  8. customthe solvent has been evaporated
  9. customto give the product
  10. custom557.03 g 2.64 min (5 min run)

Sources & evidence

ORD record
ord-3299c800fa104b89b1d12a93d3a8321b
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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