1-Phenoxy-2-propanamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-phenoxy-ethyl)-amide

HRID 246208Notes

Reaction equation

HRID 246208 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:34][C:35]1[CH:43]=[C:42]2[C:38]([C:39]([C:45]3[N:46]=[C:47]4[C:53]([C:54]([OH:56])=O)=[CH:52][N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62])[C:48]4=[N:49][CH:50]=3)=[N:40][N:41]2[CH3:44])=[CH:37][CH:36]=1.[O:65]([CH2:72][CH:73]([NH2:75])[CH3:74])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.C([O-])(O)=O.[Na+]>CCOC(C)=O.CN(C=O)C>[CH3:74][CH:73]([NH:75][C:54]([C:53]1[C:47]2[C:48](=[N:49][CH:50]=[C:45]([C:39]3[C:38]4[C:42](=[CH:43][C:35]([F:34])=[CH:36][CH:37]=4)[N:41]([CH3:44])[N:40]=3)[N:46]=2)[N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:62])[CH3:63])[CH:52]=1)=[O:56])[CH2:72][O:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

8

Reactant 5

HCID 370871-Phenoxy-2-propanamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712859942-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-phenoxy-ethyl)-amideYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In a 100 mL round-bottomed flask, HBTU (78 mg, 0.21 mmol), Hunig's base (0.14 ml, 0.79 mmol) and 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (70 mg, 0.16 mmol) were combined with DMF (3 ml) to give a light yellow solution. 1-Phenoxypropan-2-amine (48 mg, 0.32 mmol) was added and the reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with EtOAc. The reaction mixture was poured into 50 mL sat NaHCO3 and extracted with EtOAc (2×50 mL). The organic layers were combined and washed with water (2×50 mL) then dried over MgSO4 and concentrated in vacuo to provide 81 mg (89%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-phenoxy-ethyl)-amide as a white solid. MS: (M+H)+=575.

Workup

  1. customto give a light yellow solution
  2. additionThe reaction mixture was poured into 50 mL
  3. extractionextracted with EtOAc (2×50 mL)
  4. washwashed with water (2×50 mL)
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5151fb9abab6470e9e32201630f6ca80
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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