Morpholine → HCID 17990076, compound

HRID 1292964Notes

Reaction equation

HRID 1292964 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:9]=[C:10]([NH:22][C:23]2[C:24]3[C:31]4[CH2:32][CH2:33][CH:34]([CH2:36][CH2:37]OS(C)(=O)=O)[CH2:35][C:30]=4[S:29][C:25]=3[N:26]=[CH:27][N:28]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.CCN(C(C)C)C(C)C.CO.C(Cl)Cl>C(#N)C>[Cl:7][C:8]1[CH:9]=[C:10]([NH:22][C:23]2[C:24]3[C:31]4[CH2:32][CH2:33][CH:34]([CH2:36][CH2:37][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[CH2:35][C:30]=4[S:29][C:25]=3[N:26]=[CH:27][N:28]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 17990097HCID 17990097, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 17990076HCID 17990076, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Morpholine (0.03 mL, 26. mg, 0.30 mmol, 1.2 equiv.) was added to a suspension of Methanesulfonic acid 2-{4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-7-yl}-ethyl ester (135 mg, 0.25 mmol, 1 quiv.) and DIEA (0.09 mL, 0.5 mmol, 2 equiv.) in anhydrous acetonitrile (2.0 mL). The resulting mixture was stirred overnight at 80° C. at which time TLC (MeOH/DCM 5:95) indicated no more starting material left. The solvents were evaporated and residue was purified by preparative TLC (20 cm×20 cm×1 mm silica, MeOH/DCM 5:95) to give [3-Chloro-4-(pyridin-2-ylmethoxy)-phenyl]-[7-(2-morpholin-4-yl-ethyl)-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-4-yl]-amine as a white solid (16 mg, 12%). 1H-NMR (CD3OD) δ 8.51 (s, 1H), 8.24 (s, 1H), 7.87 (t, 1H), 7.81 (d, J=2.4 Hz, 1H) 7.68 (d, J=7.5 Hz, 1H), 7.36 (m, 2H), 7.02 (d, J=9.2 Hz, 1H), 5.18 (s, 2H), 2.69 (t, 4H), 3.35 (s, 1H), 3.11 (m, 1H), 3.02 (m, 1H), 2.91 (m, 1H), 2.48 (m, 6H), 2.09 (m, 1H), 1.89 (m, 1H), 1.62 (m, 3H).; LCMS RT=2.25 min; [M+H]+=536.

Workup

  1. waitleft
  2. customThe solvents were evaporated
  3. customresidue was purified by preparative TLC (20 cm×20 cm×1 mm silica, MeOH/DCM 5:95)

Sources & evidence

ORD record
ord-65f9175544424ea0a15ccaf8b45e8cd1
Source dataset
uspto-grants-2007_07
Patent number
US07238701B2

Reaction notes

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