Hydrochloric Acid → HCID 67263670, compound

HRID 1040883Notes

Reaction equation

HRID 1040883 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:18])[CH3:17])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:34]=[CH:33][C:24]2[NH:25][C:26](=[O:32])[CH2:27][CH2:28][C:29]([CH3:31])([CH3:30])[C:23]=2[CH:22]=1.Cl>O1CCOCC1.COCCO>[Cl:19][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:18])[CH3:17])=[N:7][C:2]([NH:20][C:21]2[CH:34]=[CH:33][C:24]3[NH:25][C:26](=[O:32])[CH2:27][CH2:28][C:29]([CH3:31])([CH3:30])[C:23]=3[CH:22]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 578538307-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86633890HCID 86633890, compound

Product 1

HCID 67263670HCID 67263670, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-acetamide (96 mg, 0.317 mmol), 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (81 mg, 0.397 mmol), 4 N HCl in dioxane (100 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 7 hours. Evaporated off solvent and purified with normal phase chromatography eluting with 97/3/1 CH2Cl2/MeOH/NH4OH to yield an off-white solid, N-{(1R,2R)-2-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-acetamide (54 mg, 36%). mp 227° C.; LCMS: m/z=471.38 (M+H+), 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.71 (dd, 1H, J=8.6, 2.3 Hz), 7.32 (m, 1H), 6.91 (d, 1H, J=8.6 Hz), 6.81 (m, 1H), 6.13 (m, 1H), 3.79 (m, 2H), 3.20 (s, 1H), 2.35 (m, 2H), 2.25 (m, 1H), 2.11 (m, 2H), 2.04 (m, 1H), 1.81 (m, 8H), 1.36 (m, 8H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 7 hours
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography
  5. washeluting with 97/3/1 CH2Cl2/MeOH/NH4OH

Sources & evidence

ORD record
ord-48ccc3fb31fc4bfaa0c556d272840ccf
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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