Methanol → 1-(4-(4-(4-(2-Aminophenoxy)-5-chloropyrimidin-2-ylamino)-3-methoxy phenyl)piperazin-1-yl)ethanone

HRID 2284907Notes

Reaction equation

HRID 2284907 reaction equation
[Cl:1][C:2]1[C:3]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N+:33]([O-])=O)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:23])[CH3:22])[CH2:17][CH2:16]3)=[CH:11][C:10]=2[O:24][CH3:25])=[N:6][CH:7]=1.O.[Cl-].[NH4+].CO>O1CCOCC1.C(Cl)(Cl)Cl.[Zn]>[NH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[O:26][C:3]1[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:23])[CH3:22])[CH2:17][CH2:16]3)=[CH:11][C:10]=2[O:24][CH3:25])[N:4]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 962WaterHCID 25517Ammonium ChlorideHCID 86729634HCID 86729634, compound

Product 1

HCID 867296351-(4-(4-(4-(2-Aminophenoxy)-5-chloropyrimidin-2-ylamino)-3-methoxy phenyl)piperazin-1-yl)ethanone

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 1-(4-(4-(5-chloro-4-(2-nitrophenoxy)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazin-1-yl)ethanone (140 mg, 0.28 mmol) in 1,4-dioxane:water (10 mL:4 mL), Zinc dust (81 mg, 1.4 mmol) and ammonium chloride (74 mg, 1.4 mmol) were added, and the mixture was stirred at rt for 30 min. TLC showed completion of starting material (TLC system:5% methanol in chloroform (Rf): 0.3). The reaction mixture was filtered, concentrated, diluted with water (20 mL) and extracted with ethyl acetate (3×10 mL). The organic layer was separated, dried over sodium sulphate, and concentrated. Crude compound was washed with n-pentane to obtain 1-(4-(4-(4-(2-aminophenoxy)-5-chloropyrimidin-2-ylamino)-3-methoxy phenyl)piperazin-1-yl)ethanone as a pale yellow solid. (Yield: 90 mg, 68.7%). 1HNMR (DMSO-d6) δ 8.30 (s, 1H), 7.90 (s, 1H), 7.35 (d, 1H), 7.00 (m, 2H), 6.80 (d, 1H), 6.58 (m, 2H), 6.20 (br s, 1H), 4.90 (br s, 2H), 3.75 (s, 3H), 3.55 (m, 4H), 3.05 (m, 2H), 2.95 (m, 2H), 2.02 (s, 3H). Step-4. Preparation of N-(2-(2-(4-(4-acetylpiperazin-1-yl)-2-methoxyphenylamino)-5-chloro pyrimidin-4-yloxy)phenyl)acrylamide:

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. additiondiluted with water (20 mL)
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated
  8. washCrude compound was washed with n-pentane

Sources & evidence

ORD record
ord-6c53ac7757f14280b424accb92e39574
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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