Dimethylamine → N-((1R,2S)-1-(1-(4-((dimethylamino)methyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)-2,2,2-trifluoroacetamide

HRID 13179Notes

Reaction equation

HRID 13179 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]([NH:5][C@@H:6]([CH3:32])[C@H:7]([O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30]O)=[CH:26][CH:25]=1)[N:19]=[CH:18]2)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[CH2:35]([N:37](CC)[CH2:38]C)C.CS(Cl)(=O)=O.CNC>[Cl-].[Na+].O.ClCCl>[CH3:35][N:37]([CH2:30][C:27]1[CH:26]=[CH:25][C:24]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([O:14][C@H:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:6]([NH:5][C:3](=[O:4])[C:2]([F:34])([F:33])[F:1])[CH3:32])=[CH:23][CH:22]=3)[CH:18]=[N:19]2)=[CH:29][CH:28]=1)[CH3:38]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59339791HCID 59339791, compound

Product 1

HCID 59339629N-((1R,2S)-1-(1-(4-((dimethylamino)methyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)-2,2,2-trifluoroacetamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred, ice-cooled suspension of 2,2,2-trifluoro-N-((1R,2S)-1-(1-(4-(hydroxymethyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)acetamide (141, 118 mg, 0.25 mmol) and triethylamine (0.35 mL, 2.5 mmol) was added methanesulfonyl chloride (140 μL, 1.8 mmol). After stirring for 50 min at 0° C. brine and dichloromethane (10 mL) were added. The mixture was washed with aqueous KHSO4 (1M) and sat. aqueous NaHCO3. To the organic phase was added dimethylamine (0.75 mL, 11.3 mmol). The mixture was stirred at ambient temperature for 40 min and was then evaporated. Preparative HPLC (Kromasil C-18, 2.5×20 cm, 30-90% CH3CN in water/40 min (0.1% TfA) afforded slightly impure title compound as a TfA-salt. The material was dissolved in MeOH and absorbed on a plug of acidic ion exchange resin (SCX, 5 g, pre-washed with MeOH). Eluting subsequently with MeOH and methanolic ammonia (2M) gave somewhat impure title compound. Purification by preparative HPLC on an XBridge C-18 column using a gradient of 50-90% acetonitrile in water containing 0.1% aqueous ammonia (28%). afforded pure N-((1R,2S)-1-(1-(4-((dimethylamino)methyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)-2,2,2-trifluoroacetamide (77 mg, 61%).

Workup

  1. temperatureTo a stirred, ice-cooled
  2. additionwere added
  3. washThe mixture was washed with aqueous KHSO4 (1M) and sat. aqueous NaHCO3
  4. customwas then evaporated

Sources & evidence

ORD record
ord-e60db255636348b88ba5b56379604c90
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Reaction notes

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