HCID 59733734, compound → HCID 11590854, compound

HRID 132112Notes

Reaction equation

HRID 132112 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH:11]2[CH2:13][O:12]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[C:14]([C:18]1[CH:19]=[C:20]([C:24]2([NH2:34])[CH2:32][CH2:31][C:30]3[C:26](=[CH:27][N:28]([CH3:33])[N:29]=3)[CH2:25]2)[CH:21]=[CH:22][CH:23]=1)([CH3:17])([CH3:16])[CH3:15]>C(O)(C)C>[NH4+:28].[OH-:12].[C:14]([C:18]1[CH:19]=[C:20]([C:24]2([NH:34][CH2:13][CH:11]([OH:12])[CH2:10][CH2:9][C:4]3[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=3)[CH2:32][CH2:31][C:30]3[C:26](=[CH:27][N:28]([CH3:33])[N:29]=3)[CH2:25]2)[CH:21]=[CH:22][CH:23]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 2

HCID 59733734HCID 59733734, compoundHCID 59733737HCID 59733737, compound

Product 2

HCID 14923Ammonium HydroxideHCID 11590854HCID 11590854, compoundYield 61.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

To a sealed tube was added 2-[2-(3,5-difluoro-phenyl)-ethyl]-oxirane (0.124 g, 0.673 mmol) and 5-(3-tert-butyl-phenyl)-2-methyl-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (0.174 g, 0.614 mmol) in a solution of isopropyl alcohol (2.5 mL). The reaction mixture was heated at 120° C. for 4 h and concentrated to yield crude product. The crude product was purified by flash chromatography, eluting with 50% hexane in ethyl acetate, 5% CH3OH in CH2Cl2 and conc. NH4OH to afford 0.089 g (0.19 mmol, 31%) of the 1-[5-(3-tert-butyl-phenyl)-2-methyl-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-4-(3,5-difluoro-phenyl)-butan-2-ol 2. HPLC purification afforded the trifluoroacetic acid salt: retention time (min)=1.80, method [1]; 1H NMR (300 MHz, CD3OD): δ 7.60 (d, J=2 Hz, 1H), δ 7.59-7.27 (m, 4H), δ 6.81-6.75 (m, 3H), δ 3.81 (s, 3H), δ 3.75 (m, 1H), δ 3.70 (s, 2H), δ 3.09-3.02 (m, 2H), δ 2.88-2.04 (m, 6H), δ 1.71-1.61 (m, 1H), δ 1.37 (m, 2H), δ 1.28 (s, 9H); MS (ESI) 468.3 (M+H).

Workup

  1. concentrationconcentrated
  2. customto yield crude product
  3. customThe crude product was purified by flash chromatography
  4. washeluting with 50% hexane in ethyl acetate, 5% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-b6a370cb874f4ec7b7f7c9924a0123d8
Source dataset
uspto-grants-2008_06
Patent number
US07385085B2

Reaction notes

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