Reaktion #636633

ord-3dcbc57316c04dd188bdc20de950504c

Reaktionsgleichung

O=C(O)c1cc2cc(F)ccc2[nH]1
5-fluoro-1H-indole-2-carboxylic acid
CC1(C)Cc2ccc(C#N)cc2[C@@H]1N
(R)-3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carbonitrile
CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.F[P-](F)(F)(F)(F)F
BOP reagent
CN1CCOCC1
N-methylmorpholine
CC1(C)Cc2ccc(C#N)cc2[C@@H]1NC(=O)c1cc2cc(F)ccc2[nH]1
desired title product
Ausbeute 76.6%
CC1(C)Cc2ccc(C#N)cc2[C@@H]1NC(=O)c1cc2cc(F)ccc2[nH]1
(R)—N-(6-Cyano-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)-5-fluoro-1H-indole-2-carboxamide
Ausbeute 76.6%

Lösungsmittel

Reaktionsbedingungen

Temperatur
50°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Vorschrift

A mixture of 5-fluoro-1H-indole-2-carboxylic acid (56.0 mg, 0.312 mmol), (R)-3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carbonitrile (39.0 mg, 0.209 mmol), BOP reagent (180 mg, 0.407 mmol), N-methylmorpholine (0.13 mL, 1.18 mmol) in DMF (0.5 mL) was stirred at 50° C. for 2 hr. The desired title product (55.6 mg, 76% yield) was isolated as a white solid by prep. HPLC. LCMS (M+H)+=348.33. 1H NMR (500 MHz, DMSO-d6) δ: 11.7 (s, 1H), 8.58 (d, J=8.8 Hz, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.62 (s, 1H), 7.46 (d, J=7.7 Hz, 1H), 7.44 (dd, J=8.8, 5.0 Hz, 1H), 7.39 (d, J=9.9 Hz, 1H), 7.28 (s, 1H), 7.04 (t, J=9.35 Hz, 1H), 5.37 (d, J=9.35 Hz, 1H), 2.87 (dd, J=22.0, 16.5 Hz, 2H), 1.21 (s, 3H), 0.94 (s, 3H).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07943658B2uspto-grants-2011_05