Hydrochloric Acid → 7-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one

HRID 1687190Notes

Reaction equation

HRID 1687190 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][C:10]=2[O:21][CH3:22])[C:5]([Cl:23])=[CH:4][N:3]=1.[NH2:24][C:25]1[CH:38]=[CH:37][C:28]2[NH:29][C:30](=[O:36])[CH2:31][CH2:32][C:33]([CH3:35])([CH3:34])[C:27]=2[CH:26]=1.Cl.O1CCO[CH2:42][CH2:41]1>COCCO>[Cl:23][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][C:10]=2[O:21][CH3:22])=[N:7][C:2]([NH:24][C:25]2[CH:38]=[CH:37][C:28]3[N:29]([CH2:41][CH3:42])[C:30](=[O:36])[CH2:31][CH2:32][C:33]([CH3:35])([CH3:34])[C:27]=3[CH:26]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 578538307-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86633851(2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine

Product 1

HCID 672640807-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneYield 51%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

Combined (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (108 mg, 0.304 mmol), 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (79 mg, 0.387 mmol), 4 N HCl in dioxane (100 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 2 hours. Evaporated off solvent and purified with normal phase chromatography to yield an off-white solid, 7-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (81 mg, 51%). mp 255° C.; LCMS: m/z=523.06 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.21 (d, 1H, J=7.6 Hz), 8.04 (d, 1H, J=1.5 Hz), 7.65 (d, 1H, J=8.3 Hz), 7.61 (s, 1H), 7.37 (s, 1H), 7.15 (s, 1H), 6.96 (s, 1H), 6.87 (d, 1H, J=8.6 Hz), 6.56 (s, 1H), 6.49 (d, 1H, J=8.8 Hz), 3.94 (s, 3H), 3.91 (m, 4H), 3.17 (m, 4H), 2.41 (m, 2H), 2.12 (m, 2H), 1.40 (s, 6H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 2 hours
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-1d2d628add30465995c3d73b3d542334
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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