Trifluoroacetic acid → HCID 71288650, compound

HRID 246046Notes

Reaction equation

HRID 246046 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:48])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH:33]5[CH2:37][O:36]C(C)(C)[O:34]5)[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:48])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH:33]([OH:34])[CH2:37][OH:36])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712889132-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 71288650HCID 71288650, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (crude from Step 2) in CH2Cl2 (3 mL) was added TFA (1 mL). The reaction mixture was stirred at room temperature for 48 h then concentrated. The residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL) and stirred at room temperature for 3 h. The reaction mixture was concentrated and the residue was purified by silica gel chromatography with 0% to 10% MeOH/CH2Cl2 to afford 22 mg (20%, 2 steps) of 2-[6-Chloro-1-(2,3-dihydroxy-propyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white solid. MS: (M+Na)+=545; mp=165-180° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.14 (s, 1H), 8.69 (d, J=8.7 Hz, 1H), 8.47 (d, J=7.6 Hz, 2H), 7.91 (s, 1H), 7.23 (d, J=6.8 Hz, 1H), 5.15 (d, J=5.3 Hz, 1H), 5.03 (dd, J=5.3, 3.0 Hz, 1H), 4.84 (t, J=5.5 Hz, 1H), 4.35-4.80 (m, 5H), 4.18-4.26 (m, 1H), 3.93-4.15 (m, 2H), 3.79-3.90 (m, 1H), 3.34-3.49 (m, 2H), 1.33-1.45 (m, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL)
  3. stirringstirred at room temperature for 3 h
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was purified by silica gel chromatography with 0% to 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-3467db1ede5e4e249c1aa2ab56ea75ac
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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