Hydrochloric Acid → HCID 59586550, compound

HRID 241196Notes

Reaction equation

HRID 241196 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[CH:29][C:30]6[N:34]=[C:33]([NH:35]C(=O)OC)[NH:32][C:31]=6[CH:40]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.Cl>CO.[OH-].[K+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[CH:29][C:30]6[N:34]=[C:33]([NH2:35])[NH:32][C:31]=6[CH:40]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 59586567HCID 59586567, compound

Product 1

HCID 59586550HCID 59586550, compoundYield 54.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14797Potassium HydroxideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate (example 2) (60 mg, 0.11 mmol) in methanol and 2M potassium hydroxide (1:1, 2 mL) was stirred at 65° C. for 18 hours. The reaction mixture was cooled, adjusted to pH 10 with 2M hydrochloric acid, concentrated, diluted with ethyl acetate (10 mL), washed with brine solution (5 mL), dried over sodium sulfate, filtered, concentrated. The residue was purified by preparative reverse phase HPLC to give 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine (29 mg, 54% yield). 1H NMR (400 MHz, Methanol-d4): 8.44 (1H), 7.37 (dd, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.14 (dd, 1H), 7.07-7.01 (m, 2H), 6.99 to 6.91 (m, 3H), 6.70 (br, 1H), 4.49 (s, 2H), 4.26 (m, 2H), 3.95 (s, 2H), 3.86 (m, 2H), 2.19 (s, 3H), MS (EI) for C28H25FN6O: 481 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. additiondiluted with ethyl acetate (10 mL)
  4. washwashed with brine solution (5 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-0cb34c5aea7a4293b0a8935269b6e88b
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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