Isopropanol → HCID 66830516, compound

HRID 1041685Notes

Reaction equation

HRID 1041685 reaction equation
C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[NH2:16][C:17]1[CH:18]=[CH:19][C:20]2[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[NH:22][C:21]=2[CH:28]=1.[CH:29]1([CH2:32][NH:33][C:34](=[O:51])[C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=2[NH:42][C:43]2[C:48]([Cl:49])=[CH:47][N:46]=[C:45](Cl)[N:44]=2)[CH2:31][CH2:30]1.C(O)(C)C>C(#N)C.O>[Cl:49][C:48]1[C:43]([NH:42][C:36]2[C:37]([F:41])=[CH:38][CH:39]=[CH:40][C:35]=2[C:34]([NH:33][CH2:32][CH:29]2[CH2:31][CH2:30]2)=[O:51])=[N:44][C:45]([NH:16][C:17]2[CH:18]=[CH:19][C:20]3[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[NH:22][C:21]=3[CH:28]=2)=[N:46][CH:47]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 46151688-Amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-oneHCID 86634066HCID 86634066, compound

Product 1

HCID 66830516HCID 66830516, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

10-Camphorsulfonic acid (21 mg, 0.090 mmol), 8-Amino-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (53 mg, 0.30 mmol) and N-Cyclopropylmethyl-2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-benzamide (110 mg, 0.30 mmol) in Acetonitrile (3 mL) was irradiated in a CEM microwave (120° C., 40 min) Only partial conversion, due to poor solvation. Add Isopropyl alcohol (2 mL) and irradiate an additional 3 h, 120° C. Work up by pouring into 20 mL 1:1 water:satd. aq. sodium bicarbonate and extract with DCM (2×15 mL), wash with brine, dry over sodium sulfate and conc. onto 1 g silica gel. Chromatography (ISCO, 2×12 g silica, 0-5% MeOH:DCM) to afford 2-[5-Chloro-2-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-N-cyclopropylmethyl-3-fluoro-benzamide as an off white film (60 mg, 40%). LCMS: 495 (M+H); 1H-NMR (DMSO): 9.32 (s, 1H), 9.25 (s, 1H), 9.13 (s, 1H), 8.49 (m, 1H), 8.16 (s, 1H), 7.45 (m, 2H), 7.38 (m, 1H), 7.19 (d, 1H, J=8.4 Hz), 7.09 (s, 1H), 6.92 (d, 1H, J=8.2 Hz), 3.31 (s, 2H), 3.07 (t, 2H, J=6.0 Hz), 2.55 (m, 2H), 2.03 (m, 4H), 0.89 (m, 1H), 0.35 (m, 2H), 0.14 (m, 2H); 19F-NMR (DMSO): −115.

Workup

  1. extractionaq. sodium bicarbonate and extract with DCM (2×15 mL)
  2. washwash with brine
  3. dry with materialdry over sodium sulfate and conc. onto 1 g silica gel

Sources & evidence

ORD record
ord-583abf4aa1b449ada07259ec9e951ce7
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…