Isopropanol → 2-{5-Chloro-2-[1-(2-methoxy-ethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide

HRID 1687155Notes

Reaction equation

HRID 1687155 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[N:31]([CH2:32][CH2:33][O:34][CH3:35])[C:30](=[O:36])[CH2:29][CH2:28][CH2:27][C:26]=2[CH:37]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(O)(C)C>O>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[N:31]([CH2:32][CH2:33][O:34][CH3:35])[C:30](=[O:36])[CH2:29][CH2:28][CH2:27][C:26]=3[CH:37]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 434466107-Amino-1-(2-methoxyethyl)-1,3,4,5-tetrahydrobenzo[b]azepin-2-oneHCID 717421912-(2,5-Dichloropyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

Product 1

HCID 668303752-{5-Chloro-2-[1-(2-methoxy-ethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamideYield 48%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vessel was charged with 2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (50.0 mg, 0.159 mmol), 7-amino-1-(2-methoxy-ethyl)-1,3,4,5-tetrahydro-1-benzazepin-2-one (45 mg, 0.19 mmol), 10-camphorsulfonic acid (5.0 mg, 0.022 mmol) and isopropyl alcohol (2 mL) and heated at 120° C. for 30 minutes in a microwave reactor (sealed vessel). The reaction was diluted with water (10 mL) and extracted into EtOAc. The organic layer was washed with NaHCO3 and dried by passing through a funnel filled with MgSO4. The filtrate was evaporated and the residue purified by chromatography (silica gel, 5% NH4OH in MeOH gradient with DCM). The appropriate fractions were combined and evaporated to afford a solid that was triturated with ether (2×2 mL) and yielded product (39.0 mg, 48%) as a white powder that had the following properties: m.p.=146-147° C., bubbled, remelt at 184-187° C.; LC/MS (ESI+): 513 (M+H); 1H-NMR (CDCl3, 400 MHz): δ 8.90 (s, 1H), 8.10 (s, 1H), 7.4-7.2 (m, 5H), 7.10 (d, J=8.5, 1H), 7.0 (s, 1H), 6.2, (s, 1H), 3.7-4.2 (m, 2H), 3.55-3.47 (m, 2H), 3.30 (s, 3H), 2.95 (d, J=4.9, 3H), 2.9-2.4 (m, 2H), 2.3-2.2 (m, 2H), 1.8-2.3 (m, 2H).

Workup

  1. custom(sealed vessel)
  2. extractionextracted into EtOAc
  3. washThe organic layer was washed with NaHCO3
  4. customdried
  5. customby passing through a funnel
  6. additionfilled with MgSO4
  7. customThe filtrate was evaporated
  8. customthe residue purified by chromatography (silica gel, 5% NH4OH in MeOH gradient with DCM)
  9. customevaporated
  10. customto afford a solid
  11. customthat was triturated with ether (2×2 mL)

Sources & evidence

ORD record
ord-4bf42e1715164b0f9ccb1ccfd1864f4c
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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