1-Butanol → 1-(4-((4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)methyl)-1H-indol-3-yl)-2,2,2-trifluoroethanone

HRID 475251

Reaction equation

HRID 475251 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[NH:13][N:12]=[C:11]([CH:14]3[CH2:16][CH2:15]3)[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[NH:17]1[C:25]2[C:20](=[C:21]([CH2:26][NH2:27])[CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18]1.CCN(C(C)C)C(C)C.CCCCO.[C:42](O)([C:44]([F:47])([F:46])[F:45])=[O:43]>>[CH:14]1([C:11]2[NH:12][N:13]=[C:9]([NH:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:27][CH2:26][C:21]4[CH:22]=[CH:23][CH:24]=[C:25]5[C:20]=4[C:19]([C:42](=[O:43])[C:44]([F:47])([F:46])[F:45])=[CH:18][NH:17]5)[N:7]=3)[CH:10]=2)[CH2:16][CH2:15]1

Participants

6

Reactant 5

HCID 2631-ButanolHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 280302(1H-indol-4-yl)methanamineHCID 178478345HCID 178478345, compound

Product 1

HCID 712727191-(4-((4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)methyl)-1H-indol-3-yl)-2,2,2-trifluoroethanone

Conditions

Temperature
70 °C

Procedure

A vial was charged with 53 (300 mg, 1.27 mmol), (1H-indol-4-yl)methanamine (279 mg, 1.903.20 mmol, CASRN 3468-18-6), DIPEA (0.67 mL) and n-BuOH (3 mL), sealed and heated at 140 C for 72 h. The reaction mixture was concentrated in vacuo, and the residue was partitioned between EtOAc and H2O. The aqueous layer was extracted once with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude produce was directly dissolved in TFA (3 mL), and the mixture was heated at 70° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue purified by preparative HPLC to afford 38.3 mg (7%) of I-37.

Workup

  1. customsealed
  2. temperatureheated at 140 C for 72 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was partitioned between EtOAc and H2O
  5. extractionThe aqueous layer was extracted once with EtOAc
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude produce
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. customthe residue purified by preparative HPLC
  12. customto afford 38.3 mg (7%) of I-37

Sources & evidence

ORD record
ord-7abadea4eb6a400fb02a72bd1cd89bcf
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Linked notes

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