Morpholine → HCID 59380488, compound

HRID 2353853Notes

Reaction equation

HRID 2353853 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[C:25]4[CH:26]=[CH:27][C:28]([CH2:30][C:31](O)=[O:32])=[CH:29][C:24]=4[S:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[C:25]4[CH:26]=[CH:27][C:28]([CH2:30][C:31]([N:55]5[CH2:60][CH2:59][O:58][CH2:57][CH2:56]5)=[O:32])=[CH:29][C:24]=4[S:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59380367HCID 59380367, compound

Product 1

HCID 59380488HCID 59380488, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}[1]benzothieno[2,3-d]pyrimidin-7-yl)acetic acid (50 mg, 0.10 mmol, 1 eq, from example 94) in DCM (2 mL) were added HOBt (14 mg, 0.10 mmol, 1 equiv) and EDCI (24 mg, 0.13 mmol, 1.2 equiv) under nitrogen. After the mixture was stirred at rt for 5 min, morpholine was added. The resulting reaction mixture was stirred at rt for 15 h. The solvent was concentrated in vacuo. Methanol was added to the residue and a white solid was precipitated out from the solution. The solid was filtered, washed with methanol (2×3 mL) then dried in vacuo to obtain a white solid (27.8 mg, 0.05 mmol, 51%). 1H-NMR (DMSO-d6) δ 9.0 (broad s, 1H), 8.58 (d, J=4.6 Hz, 1H), 8.51 (s, 1H), 8.49 (d, J=8.5 Hz, 1H), 7.94 (s, 1H), 7.87 (t, 1H), 7.76 (d, J=2.2 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.53 (dd, J=2.6, 8.8 Hz, 1H), 7.45 (d, J=8.5 Hz, 1H), 7.35 (m, 1H), 7.24 (d, J=8.7 Hz, 1H), 5.30 (s, 2H), 3.91 (s, 2H), 3.50 (m, 8H); LCMS RT=2.69 min, [M+H]+=546.20

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at rt for 15 h
  3. concentrationThe solvent was concentrated in vacuo
  4. additionMethanol was added to the residue
  5. customa white solid was precipitated out from the solution
  6. filtrationThe solid was filtered
  7. washwashed with methanol (2×3 mL)
  8. customthen dried in vacuo

Sources & evidence

ORD record
ord-0b0c8dd1f1b44c7895eeb69fdc3ab128
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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