Ammonia → N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]hexahydro-1H-1,4-diazepin-1-yl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419590Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH3:37][C:38]1[C:39]([N:47]2[CH2:53][CH2:52][CH2:51][N:50]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:49][CH2:48]2)=[CH:40][C:41]([O:45][CH3:46])=[C:42]([CH:44]=1)[NH2:43].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.N>CO.C(Cl)Cl>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:43][C:42]3[CH:44]=[C:38]([CH3:37])[C:39]([N:47]4[CH2:53][CH2:52][CH2:51][N:50]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:49][CH2:48]4)=[CH:40][C:41]=3[O:45][CH3:46])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]

Participants

Conditions

Temperature: 100 °C

Procedure

5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (100 mg, 0.2 mmol), 5-methyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]hexahydro-1H-1,4-diazepin-1-yl}aniline (67 mg, 0.2 mmol), and p-toluenesulfonicacid (90 mg, 0.47 mmol) were weighed into a 20 mL vial. 1 mL of trifluoroethanol was added and the mixture was heated to 100° C. for 24 h. 2 mL of 2 N ammonia in MeOH was added. The solvent was rotovaped down. The residue was taken up in 3 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-absorbed solids were purified by flash chromatography to give the title compound (94 mg, 0.12 mmol, 59%). 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 9.36 (s, 1H), 8.44 (s, 1H), 8.22 (d, J=5.13 Hz, 1H), 8.04 (d, J=2.20 Hz, 1H), 7.74 (dd, J=8.62, 2.02 Hz, 1H), 7.69 (d, J=8.80 Hz, 1H), 7.41-7.48 (m, 2H), 7.32-7.41 (m, 1H), 7.26 (d, J=8.80 Hz, 1H), 7.18 (t, J=8.07 Hz, 2H), 6.94 (t, J=6.78 Hz, 1H), 6.79 (s, 1H), 6.55 (d, J=5.13 Hz, 1H), 4.26 (q, J=6.97 Hz, 2H), 3.78 (s, 3H), 3.28 (t, J=7.15 Hz, 2H), 3.06-3.14 (m, 4H), 3.04 (s, 3H), 2.92 (t, J=6.78 Hz, 2H), 2.80 (t, J=5.68 Hz, 4H), 2.15 (s, 3H), 1.85 (qd, J=5.74, 5.50 Hz, 2H), 1.42 (t, J=6.78 Hz, 3H); MS (ESI): 811 [M+H]+.

Workup

addition1 g of silica gel was added
customthe pre-absorbed solids were purified by flash chromatography

Sources & evidence

ORD record: ord-628e2c3710204e7c896fecd666ce59c5
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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