Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-{5-chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

(S)-3-(7-Amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol (96 mg, 0.350 mmol, 1.0 eq), 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (115 mg, 0.385 mmol, 1.1 eq), and 10-camphorsulfonic acid (89 mg, 0.385 mmol, 1.1 eq) were dissolved in IPA (3 mL) and heated at 120° C. in a microwave for 40 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by amine capped silica gel chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain 2-{5-chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide as a pale yellow solid (101 mg, 54%). LCMS (m/e) 535 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.09 (s, 1H), 8.67 (d, 1H, J=8.4 Hz), 8.11 (s, 1H), 7.51 (d, 1H, J=7.8 Hz), 7.48-7.42 (m, 1H), 7.40 (s, 1H), 7.31-7.26 (m, 1H), 7.14-7.08 (m, 1H), 7.05 (d, 1H, J=8.0 Hz), 6.91 (s, 1H), 6.21 (bs, 1H), 4.42 (bs, 1H), 4.10-4.02 (m, 1H), 3.05 (d, 3H, J=4.6 Hz), 3.00-2.80 (m, 7H), 2.78-2.64 (m, 3H).

Provenance & Evidence