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 1040878Notes

Reaction equation

HRID 1040878 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:40]=[CH:39][C:28]2[N:29]([CH2:37][CH3:38])[C:30](=[O:36])[CH2:31][CH2:32][C:33]([CH3:35])([CH3:34])[C:27]=2[CH:26]=1.Cl>O1CCOCC1.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:40]=[CH:39][C:28]3[N:29]([CH2:37][CH3:38])[C:30](=[O:36])[CH2:31][CH2:32][C:33]([CH3:34])([CH3:35])[C:27]=3[CH:26]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 672637817-Amino-1-ethyl-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 92.3%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (113 mg, 0.3185 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (74 mg, 0.3185 mmol), 4 N HCl in dioxane (100 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 3 hours. Evaporated off solvent and purified with normal phase chromatography to yield a yellow 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 (162 mg, 92%). LCMS: m/z=551.00 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.21 (d, 1H, J=9.4 Hz), 8.04 (s, 1H), 7.69 (d, 1H, J=9.4 Hz), 7.60 (s, 1H), 7.34 (s, 1H), 7.19 (d, 1H, J=8.1 Hz), 6.92 (s, 1H), 6.56 (s, 1H), 6.49 (d, 1H, J=8.6 Hz), 3.94 (s, 3H), 3.90 (m, 4H), 3.82 (m, 2H), 3.16 (m, 4H), 2.32 (m, 2H), 2.06 (m, 2H), 1.33 (m, 9H).

Workup

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

Sources & evidence

ORD record
ord-d1839be4798842a2824f3dfc87e7d45b
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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