Dimethylformamide → HCID 67389031, compound

HRID 1958361Notes

Reaction equation

HRID 1958361 reaction equation
[N:1]1([C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:31])[C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]3[CH:21]=[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=4)[N:23]=[C:17]3[N:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1.[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[N:1]1([C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:31])[C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]3[CH:21]=[C:22]([C:24]4[CH:25]=[C:26]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH:27]=[CH:28][CH:29]=4)[N:23]=[C:17]3[N:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 67384213HCID 67384213, compound

Product 1

HCID 67389031HCID 67389031, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

Under an atmosphere of argon, in a 25 mL round-bottomed flask, 4-(azetidine-1-carbonyl)-N-(2-(3-bromophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide (85 mg, 177 μmol, Eq: 1.00, example 117), phenylboronic acid (43.2 mg, 354 μmol, Eq: 2), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (14.5 mg, 17.7 μmol, Eq: 0.1) and potassium carbonate (73.4 mg, 531 μmol, Eq: 3) were combined with DMF (2 ml) and water (0.2 ml) to give a brown solution. The reaction was stirred for 1 h at 100° C. The HPLC-MS showed complete conversion. The reaction mixture was poured into 20 mL water and extracted with EtOAc (2×25 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. After the addition of 2 ml Methanol the desired product crystallized. The suspension was filtered off and washed with 0.5 ml MeOH. The residual solvent was removed under vacuum. The title compound was obtained as a light brown solid (42 mg, 49.7%). 4-(Azetidine-1-carbonyl)-N-(2-(3-bromophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide was prepared in analogy to example 29, using 2-(3-bromo-phenyl)-imidazo[1,2-a]pyrimidin-7-ylamine in the first step. 2-(3-Bromo-phenyl)-imidazo[1,2-a]pyrimidin-7-ylamine can be prepared in analogy to example 1, step 1, from 2-bromo-1-(3-bromo-phenyl)-ethanone.

Workup

  1. customto give a brown solution
  2. extractionextracted with EtOAc (2×25 mL)
  3. dry with materialThe organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. additionAfter the addition of 2 ml Methanol the desired product
  6. customcrystallized
  7. filtrationThe suspension was filtered off
  8. washwashed with 0.5 ml MeOH
  9. customThe residual solvent was removed under vacuum

Sources & evidence

ORD record
ord-fe33b11e95ee485b985106440592959c
Source dataset
uspto-grants-2013_04
Patent number
US08410117B2

Reaction notes

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