Water → HCID 178481761, compound

HRID 246329Notes

Reaction equation

HRID 246329 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:11][C@@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[NH2:7][C@@H:8]1[CH2:9][C@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH2:11]1

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 178481749HCID 178481749, compound

Product 1

HCID 178481761HCID 178481761, compoundYield 96.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round-bottomed flask, (cis-3-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclobutyl)carbamic acid tert-butyl ester (144 mg, 0.236 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.73 ml, 9.48 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was suspended in dichloromethane (1.2 ml) and ethylenediamine (0.96 ml, 14.2 mmol) was added. The light yellow suspension was stirred at room temperature for 1 h then water and ethyl acetate were added. The suspension was filtered and washed with hot water and ethyl acetate. The product was dried under high vacuum to provide 86 mg (91%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-amino-cyclobutyl)-amide as a light yellow powder. MS: (M+H)+=380; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.09 (s, 1H), 8.54 (dd, J=8.7, 5.3 Hz, 1H), 8.41 (s, 1H), 8.28 (d, J=7.6 Hz, 1H), 7.71 (dd, J=9.8, 1.9 Hz, 1H), 7.28 (td, J=9.1, 1.9 Hz, 1H), 5.54 (br. s., 2H), 4.15 (s, 3H), 4.04-4.18 (m, 1H), 3.07-3.22 (m, 1H), 2.65-2.80 (m, 2H), 1.66-1.80 (m, 2H).

Workup

  1. concentrationthen concentrated
  2. stirringThe light yellow suspension was stirred at room temperature for 1 h
  3. filtrationThe suspension was filtered
  4. washwashed with hot water and ethyl acetate
  5. customThe product was dried under high vacuum

Sources & evidence

ORD record
ord-eebc29b40d604fa5aa47e1d2a08e5659
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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