2-Aminopyrimidine → HCID 89657379, compound

HRID 930886Notes

Reaction equation

HRID 930886 reaction equation
[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][C:6]=1[C:14]1[C:15]2[CH:24]=[CH:23][NH:22][C:16]=2[C:17](=[O:21])[N:18]([CH3:20])[CH:19]=1.ClC(N(C)C)=C(C)C.[N:38]1[CH:43]=[CH:42][CH:41]=[N:40][C:39]=1[NH2:44]>O1CCCC1.CN(C)C1C=CN=CC=1>[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:44][C:39]2[N:40]=[CH:41][CH:42]=[CH:43][N:38]=2)=[O:10])=[CH:7][C:6]=1[C:14]1[C:15]2[CH:24]=[CH:23][NH:22][C:16]=2[C:17](=[O:21])[N:18]([CH3:20])[CH:19]=1

Participants

6

Reactant 3

HCID 79782-AminopyrimidineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 896573914-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)benzoic acid

Product 1

HCID 89657379HCID 89657379, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

A solution of Example 50b (24 mg, 0.06 mmol) in a 4 mL vial was dissolved in anhydrous tetrahydrofuran (1.0 mL), followed by the addition of 1-chloro-N,N,2-trimethyl-1-propenylamine (65 μL, 0.48 mmol). This was capped and placed to shake for 2 hours at ambient temperature. Then, a solution of pyrimidin-2-amine (9 mg, 0.09 mmol) in anhydrous tetrahydrofuran (0.3 mL) was added, followed by a solution of 4-(dimethylamino)pyridine (37 mg, 0.3 mmol) in anhydrous tetrahydrofuran (0.5 mL). The mixture was stirred at 60° C. for 16 hours, cooled, and concentrated to dryness. The residues were dissolved in 1:1 DMSO/MeOH and purified by reverse phase HPLC (10-80% acetonitrile in 0.1% TFA water). 1H NMR (500 MHz, DMSO-d6/D2O, Temp=25° C.) δ ppm 8.73 (d, J=4.88 Hz, 2H) 8.09 (d, J=2.44 Hz, 1H) 7.95 (dd, J=8.70, 2.29 Hz, 1H) 7.42-7.48 (m, 1H) 7.41 (s, 1H) 7.32-7.38 (m, 2H) 7.27 (t, J=4.88 Hz, 1H) 7.11-7.17 (m, 1H) 6.90 (d, J=8.85 Hz, 1H) 6.32 (d, J=2.75 Hz, 1H) 3.60 (s, 3H); (ESI) m/z 474 (M+H)+.

Workup

  1. customThis was capped
  2. temperaturecooled
  3. concentrationconcentrated to dryness
  4. dissolutionThe residues were dissolved in 1:1 DMSO/MeOH
  5. custompurified by reverse phase HPLC (10-80% acetonitrile in 0.1% TFA water)

Sources & evidence

ORD record
ord-7f3562027810467aaa00d8cac09c626d
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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