Methanol → HCID 178433183, compound

HRID 241202Notes

Reaction equation

HRID 241202 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:15]3[CH2:21][C:20]4[CH:22]=[C:23]([C:26]5[N:31]=[C:30]6[NH:32][C:33]([NH:35]C(=O)OC)=[N:34][C:29]6=[CH:28][CH:27]=5)[CH:24]=[CH:25][C:19]=4[O:18][CH2:17][CH2:16]3)=[N:11][CH:12]=[N:13][CH:14]=2)=[CH:4][CH:3]=1.[OH-].[K+].[CH3:42]O>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:15]3[CH2:21][C:20]4[CH:22]=[C:23]([C:26]5[N:31]=[C:30]6[NH:32][C:33]([NH2:35])=[N:34][C:29]6=[CH:28][CH:27]=5)[CH:24]=[CH:25][C:19]=4[O:18][CH2:17][CH2:16]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:42])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 178502017HCID 178502017, compound

Product 1

HCID 178433183HCID 178433183, compoundYield 46%

Conditions

Temperature
100 °C

Procedure

To a solution of methyl [5-(4-{5-[(4-fluorophenyl)methyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3H-imidazo[4,5-b]pyridine-2-yl]carbamate (0.70 g, 0.129 mmol) in methanol (3 mL) was added 2 M aqueous potassium hydroxide (3 mL) and the mixture was heated at 100° C. for 1 hour. After cooling to room temperature the reaction mixture was concentrated and then diluted with water (5 mL) and the pH adjusted to 9 with 1 M hydrochloric acid. The resulting precipitate was collected by filtration, dissolved in a minimum of methanol and purified by preparative reverse phase HPLC to afford 5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3H-imidazo[4,5-b]pyridin-2-amine (0.0283 g, 46% yield. 1H NMR (400 MHz, methanol-d4): 8.45 (s, 1H), 7.75 (d, 1H), 7.51 (d, 1H), 7.17 (d, 1H), 7.11-7.06 (m, 3H), 7.01-6.96 (m, 3H), 4.55 (s, 2H), 4.30 (t, 2H), 4.00 (s, 2H), 3.89 (t, 2H), 2.22 (s, 3H); MS (EI) for C27H24FN7O: 482 (MH+)

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. concentrationwas concentrated
  3. additiondiluted with water (5 mL)
  4. filtrationThe resulting precipitate was collected by filtration
  5. dissolutiondissolved in a minimum of methanol
  6. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-4275ec3bef05434fae27e38573b9cd06
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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