Hydrochloric Acid → HCID 67264231, compound

HRID 1041018Notes

Reaction equation

HRID 1041018 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH:11]([NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:12][CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[NH2:19].Cl[C:21]1[N:26]=[C:25]([NH:27][C@@H:28]2[C@@H:33]3[CH2:34][C@@H:30]([CH:31]=[CH:32]3)[C@@H:29]2[C:35]([NH2:37])=[O:36])[C:24]([Cl:38])=[CH:23][N:22]=1.Cl.O1CCOCC1.C(=O)(O)[O-].[Na+]>COCCO>[Cl:38][C:24]1[C:25]([NH:27][C@@H:28]2[C@@H:33]3[CH2:34][C@@H:30]([CH:31]=[CH:32]3)[C@@H:29]2[C:35]([NH2:37])=[O:36])=[N:26][C:21]([NH:19][C:4]2[CH:5]=[CH:6][C:7]3[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:10][CH2:9][C:8]=3[C:3]=2[O:2][CH3:1])=[N:22][CH:23]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 57522618HCID 57522618, compoundHCID 57522620HCID 57522620, compound

Product 1

HCID 67264231HCID 67264231, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
130 °C

Procedure

1-Methoxy-N*7*-(2-methoxy-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine 200 mg, 0.8 mmol) and (1S,2S,3R,4R)-3-(2,5-dichloro-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (224 mg, 0.750 mmol) were dissolved in 5 ml 2-methoxyethanol in a reaction tube. 4N HCl in dioxane (0.4 ml, 1.6 mmol) was charged and the reaction heated to 130° C. The reaction was followed by HPLC. Upon completion, the reaction was poured into saturated sodium bicarbonate (50 ml) and extracted with methylene chloride (4×25 ml portions). The combined organic was dried over magnesium sulfate, filtered and evaporated. Purification was carried via preparative HPLC and the desired fractions neutralized and extracted to yield (1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (58.19 mg, 27% yield) as the beige foam free base. Purification separated the compound into its corresponding enantiomers. 1H-NMR (CDCl3) δ 8.17 (d, J=8.3 Hz, 1H), 7.88 (s, 1H), 7.39 (s, 1H), 6.94 (m, 1H), 6.86 (d, J=8.4 Hz, 1H), 6.37 (m, 1H), 6.31 (m, 1H), 5.61 (br s, 1H), 5.36 (br s, 1H), 4.37 (m, 1H), 3.72 (s, 3H), 3.51 (m, 2H), 3.26 (s, 3H), 3.23 (m, 1H), 3.06 (s, 1H), 2.94 (s, 1H), 2.85-2.70 (m, 6H), 2.49 (d, J=8.4 Hz, 2H), 2.24 (d, J=8.9 Hz, 1H), 2.09 (m, 2H), 1.63 (m, 2H), 1.26 (m, 4H). LC/MS (ESI+)=527 (M+H).

Workup

  1. extractionextracted with methylene chloride (4×25 ml portions)
  2. dry with materialThe combined organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customPurification
  6. extractionextracted

Sources & evidence

ORD record
ord-4e3ce757c0b8462587d89372b27d63a8
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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