Hydrochloric Acid → 3-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-azepan-2-one

HRID 1040684Notes

Reaction equation

HRID 1040684 reaction equation
[CH2:1]([N:3]1[CH2:9][CH2:8][C:7]2[CH:10]=[C:11]([NH2:14])[CH:12]=[CH:13][C:6]=2[CH2:5][CH2:4]1)[CH3:2].Cl[C:16]1[N:21]=[C:20]([NH:22][CH:23]2[CH2:29][CH2:28][CH2:27][CH2:26][NH:25][C:24]2=[O:30])[C:19]([Cl:31])=[CH:18][N:17]=1.Cl.[Na]>O.CC(O)C>[Cl:31][C:19]1[C:20]([NH:22][CH:23]2[CH2:29][CH2:28][CH2:27][CH2:26][NH:25][C:24]2=[O:30])=[N:21][C:16]([NH:14][C:11]2[CH:12]=[CH:13][C:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:9][CH2:8][C:7]=3[CH:10]=2)=[N:17][CH:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5360545SodiumHCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 582551133-(2,5-Dichloropyrimidin-4-ylamino)azepan-2-one

Product 1

HCID 668300213-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-azepan-2-oneYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (75 mg 0.20 mmol), 3-(2,5-Dichloro-pyrimidin-4-ylamino)-azepan-2-one (57 mg, 0.30 mmol) and 81 μl of 4N HCl in dioxanes were combined into 1 ml IPA in a microwave tube. The reaction was heated to 120° C. for 40 minutes in the microwave. The reaction was poured into water (50 ml) and saturated sodium bicarb (90 ml) and extracted 3 times with 25 ml portions of methylene chloride. The combined organic was dried over magnesium sulfate, filtered and evaporated to a brown oil. The crude reaction was purified on a 12 g Isco silica gel column using 0-20% methanol in methylene chloride as the eluent to yield 3-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-azepan-2-one (22.33 mg, 19%). MP: 232-234° C.; 1H-NMR (CDCl3) δ 7.99 (s, 1H), 7.47 (d, J=8 Hz, 1H), 7.16 (s, 1H), 7.08 (d, J=8 Hz, 1H), 6.97 (s, 1H), 6.83 (d, J=6 Hz, 1H), 6.30 (br s, 1H), 4.69 (q, J=9.9, 5.56 Hz, 1H), 3.32 (m, 2H), 2.92 (m, 4H), 2.72-2.52 (m, 6H), 2.25 (d, J=3.9 Hz, 1H), 2.05 (d, J=4.2 Hz, 1H), 1.95-1.65 (m, 2H), 1.60-1.40 (m, 2H), 1.08 (t, J=7 Hz, 3H); LC/MS (ESI+): 429 (M+H).

Workup

  1. extractionextracted 3 times with 25 ml portions of methylene chloride
  2. dry with materialThe combined organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated to a brown oil
  5. customThe crude reaction
  6. customwas purified on a 12 g Isco silica gel column

Sources & evidence

ORD record
ord-85e138fb605f4f0b82eba6ab7d118a20
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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