Diisopropylethylamine → HCID 178464928, compound

HRID 245995Notes

Reaction equation

HRID 245995 reaction equation
Cl.[NH2:2][CH:3]([C@@H:5]1[CH2:8][C@H:7]([OH:9])[CH2:6]1)[CH3:4].C(N(CC)C(C)C)(C)C.[F:19][C:20]1[CH:28]=[C:27]2[C:23]([C:24]([C:30]3[N:31]=[C:32]4[C:38]([C:39](O)=[O:40])=[CH:37][N:36]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:33]4=[N:34][CH:35]=3)=[N:25][N:26]2[CH3:29])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:9][C@@H:7]1[CH2:8][C@H:5]([CH:3]([NH:2][C:39]([C:38]2[C:32]3[C:33](=[N:34][CH:35]=[C:30]([C:24]4[C:23]5[C:27](=[CH:28][C:20]([F:19])=[CH:21][CH:22]=5)[N:26]([CH3:29])[N:25]=4)[N:31]=3)[N:36]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:37]=2)=[O:40])[CH3:4])[CH2:6]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)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 acidHCID 178464536HCID 178464536, compound

Product 1

HCID 178464928HCID 178464928, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of cis-3-(1-aminoethyl)-cyclobutanol hydrochloride (crude from step 6, 91 mg, 0.60 mmol) in DMF (2 mL) were added N,N-diisopropylethylamine (0.24 mL, 1.36 mmol), 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.27 mmol), and HATU (114 mg, 0.30 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated to a pale yellow solid. Trituration with EtOAc/Et2O gave 108 mg (74%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(cis-3-hydroxy-cyclobutyl)-ethyl]-amide as a white solid.

Workup

  1. customthen quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with water (3×) and brine
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated to a pale yellow solid

Sources & evidence

ORD record
ord-215f12a3fc2440d78e10de7b11af60e8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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