Potassium Phosphate, Tribasic → HCID 86729381, compound

HRID 521220Notes

Reaction equation

HRID 521220 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:44]1[CH:49]=[CH:48][N:47]=[CH:46][N:45]=1.[NH2:50][C:51]1[C:55]([C:56](=[O:58])[NH2:57])=[CH:54][N:53]([C:59]2([CH2:72][C:73]#[N:74])[CH2:64][CH2:63][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:61][CH2:60]2)[N:52]=1>CC(O)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:56]([C:55]1[C:51]([NH:50][C:44]2[CH:49]=[CH:48][N:47]=[CH:46][N:45]=2)=[N:52][N:53]([C:59]2([CH2:72][C:73]#[N:74])[CH2:64][CH2:63][N:62]([C:65]([O:67][C:68]([CH3:69])([CH3:70])[CH3:71])=[O:66])[CH2:61][CH2:60]2)[CH:54]=1)(=[O:58])[NH2:57]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 127522204-BromopyrimidineHCID 86729368tert-Butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate2×

Product 1

HCID 86729381HCID 86729381, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

K3PO4 (75 mg, 0.35 mmol), X-Phos (21 mg, 0.043 mmol), 4-bromopyrimidine (34 mg, 0.22 mmol) and tert-butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (Intermediate 35-1) (50 mg, 0.14 mmol) were suspended in t-BuOH (3 mL) and degassed with argon for 5 minutes in a microwave vial. The catalyst, Pd2(dba)3 (20 mg, 0.022 mmol), was added and then the mixture was heated at 80° C. for 2 hours. The mixture was then cooled to ambient temperature, Si-DMT (0.10 g) was added and the resulting mixture was allowed to stir for 1 hour. The mixture was filtered and passed through a C18 silica plug. The column was washed with acetonitrile (4 mL) and then the column eluent was evaporated to dryness in vacuo. The crude material was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, passed through a 6 mL Silicycle Carbonate cartridge, and lyophilized to afford the title compound, Example #13-1, as a white solid.

Workup

  1. customdegassed with argon for 5 minutes in a microwave vial
  2. temperatureThe mixture was then cooled to ambient temperature
  3. additionSi-DMT (0.10 g) was added
  4. filtrationThe mixture was filtered
  5. washThe column was washed with acetonitrile (4 mL)
  6. customthe column eluent was evaporated to dryness in vacuo
  7. customThe crude material was purified by reverse-phase preparative HPLC (MeCN/water

Sources & evidence

ORD record
ord-88f0533a68f54054a1d978bb544ae08a
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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