Hydrochloric Acid → HCID 53318635, compound

HRID 1686954Notes

Reaction equation

HRID 1686954 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:9][CH2:8][C:7]=2[CH:17]=1.Cl[C:20]1[N:25]=[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:29][C:28]=2[O:39][CH3:40])[C:23]([Cl:41])=[CH:22][N:21]=1.Cl.C(O)(C)C>O1CCOCC1>[Cl:41][C:23]1[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[CH:29][C:28]=2[O:39][CH3:40])=[N:25][C:20]([NH:18][C:4]2[C:3]([O:2][CH3:1])=[CH:17][C:7]3[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:11][CH2:12][C:6]=3[CH:5]=2)=[N:21][CH:22]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 574161508-Methoxy-3-(2-methoxyethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-amineHCID 86633851(2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine

Product 1

HCID 53318635HCID 53318635, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

Combined 8-Methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (55 mg, 0.00022 mol), (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (86 mg, 0.00024 mol), 4 M of Hydrogen chloride in 1,4-Dioxane (70 uL) and Isopropyl alcohol (2.2 mL, 0.029 mol) in microwave vessel. Heat at 130° C. for 10 minutes. Heat for another 10 minutes. Cool to room temp. Solid precipitated out of solution. Filtered off solid. The filtrate was treated with MP-carbonate 250 mgs and stirred for 30 min. The mixture was concentrated and purified by ISCO chromatography (40 g SiO2 column, gradient 100% DCM to 10% MeOH/DCM. Isolated 5-Chloro-N*2*-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine as an off-white solid (49 mgs, 39%) Melting point: 138-140° C. δ 8.30 (d, J=8.8 Hz, 1H), 8.12 (s, 1H), 8.03 (d, J=1.8 Hz, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 6.65 (s, 1H), 6.57-6.52 (m, 2H), 3.94-3.88 (m, 10H), 3.36 (br s, 2H), 3.39 (d, J=1.7 Hz, 3H), 3.18-3.17 (m, 4H), 2.90-2.74 (m, 10H); LC/MS: 568.87 (M+H).

Workup

  1. temperatureHeat for another 10 minutes
  2. temperatureCool to room temp
  3. customSolid precipitated out of solution
  4. filtrationFiltered off solid
  5. additionThe filtrate was treated with MP-carbonate 250 mgs
  6. concentrationThe mixture was concentrated
  7. custompurified by ISCO chromatography (40 g SiO2 column, gradient 100% DCM to 10% MeOH/DCM

Sources & evidence

ORD record
ord-e3667f8ed9dc432693ee7eca23eae8c1
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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