Chloride → HCID 86729640, compound

HRID 2284911Notes

Reaction equation

HRID 2284911 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:14]([C:15](=[O:17])[CH3:16])=[CH:13][N:12]=[C:11]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:21][C:20]=2[O:31][CH3:32])[N:10]=1.CCN(C(C)C)[CH:36]([CH3:38])[CH3:37].[Cl-].C[OH:44]>C(Cl)Cl>[C:15]([C:14]1[C:9]([NH:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][C:37](=[O:44])[CH:36]=[CH2:38])=[N:10][C:11]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:21][C:20]=2[O:31][CH3:32])=[N:12][CH:13]=1)(=[O:17])[CH3:16]

Participants

6

Reactant 4

HCID 312ChlorideHCID 887MethanolHCID 81531DiisopropylethylamineHCID 86729638HCID 86729638, compound

Product 1

HCID 86729640HCID 86729640, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 1-(4-(2-aminophenylamino)-2-(2-methoxy-4-morpholinophenylamino) pyrimidin-5-yl)ethanone (100 mg, 0.23 mmol) in DCM (10 ml), DIPEA (55 mg, 0.46 mmol) and acrolyl chloride (20.7 mg, 0.23 mmol) were added at −20° C., and the mixture was stirred for 30 min. TLC showed completion of starting material (TLC system: 5% methanol in DCM. (Rf): 0.5). The reaction mixture was diluted with DCM (20 mL) and washed with water (2×10 mL). The organic layer was separated, dried over sodium sulphate, and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) with 3% methanol in DCM to obtain N-(2-(5-acetyl-2-(2-methoxy-4-morpholinophenylamino) pyrimidin-4-yl amino)phenyl) acrylamide as a pale yellow solid. Yield: (30 mg, 26%). MS: m/z 489.2 (ES+); 1HNMR (DMSO-d6) δ 11.25 (s, 1H), 9.76 (s, 1H), 8.77 (s, 1H), 8.73 (s, 1H), 8.10 (br s, 1H), 7.35 (d, 1H, J=8.4 Hz), 7.25 (br s, 1H), 0.06 (br t, 2H), 6.65 (s, 1H), 6.45 (m, 2H), 6.20 (dd, 1H, J=2.0, 17.2 Hz), 5.74 (dd, 1H, J=8.0 Hz), 3.72 (m, 7H), 3.12 (m, 4H, 3.24 (br s, 3H).

Workup

  1. washwashed with water (2×10 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customCrude compound was purified by column chromatography

Sources & evidence

ORD record
ord-89ca87a6a0544fd18def5b7664348120
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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