Triethylamine → HCID 67386178, compound

HRID 1898654Notes

Reaction equation

HRID 1898654 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([C:12]1[N:13]=[C:14]3[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]3=[N:16][CH:17]=1)[C:6]2=[O:11].C(N(CC)CC)C.[NH2:39][C@H:40]([CH:49]1[CH2:51][CH2:50]1)[C:41]([N:43]1[CH2:46][CH:45]([C:47]#[N:48])[CH2:44]1)=[O:42].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:47]([CH:45]1[CH2:46][N:43]([C:41](=[O:42])[C@H:40]([NH:39][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([N:5]4[CH2:4][C:3]5[C:7](=[CH:8][CH:9]=[CH:10][C:2]=5[Cl:1])[C:6]4=[O:11])[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[CH:19]=2)=[O:23])[CH:49]2[CH2:50][CH2:51]2)[CH2:44]1)#[N:48]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 57516657HCID 57516657, compoundHCID 67386112HCID 67386112, compound

Product 1

HCID 67386178HCID 67386178, compoundYield 39.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(4-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 0.17 mmol) in DMF (2.4 mL) was added triethylamine (73 μl, 0.52 mmol), 1-((R)-2-amino-2-cyclopropyl-acetyl)-azetidine-3-carbonitrile (31.2 mg, 0.17 mmol) and PyBOP (109 mg, 0.21 mmol) at room temperature. The reaction mixture was stirred for 16 h at the same temperature then poured into EtOAc (50 mL) and washed with water (4×50 mL). The organic extracts were dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by column chromatography (SiO2, 23 g, Hex:EtOAc, 0% to 6:4, in 35 min) to afford 42 mg (39%) of 2-(4-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

Workup

  1. washwashed with water (4×50 mL)
  2. dry with materialThe organic extracts were dried (Na2SO4)
  3. customevaporated under vacuum
  4. customThe crude residue was purified by column chromatography (SiO2, 23 g, Hex:EtOAc, 0% to 6:4, in 35 min)

Sources & evidence

ORD record
ord-308aadc3fb8e40a0b5a008c808b9f9ab
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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