N,N,N',N'-Tetramethylazodicarboxamide → HCID 59380424, compound

HRID 2353841Notes

Reaction equation

HRID 2353841 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:26]4[CH:27]=[CH:28][C:29]([OH:31])=[CH:30][C:25]=4[S:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N(C)C)=O)=NC(N(C)C)=O.O[CH2:64][CH2:65][N:66]1[CH2:71][CH2:70][O:69][CH2:68][CH2:67]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:26]4[CH:27]=[CH:28][C:29]([O:31][CH2:64][CH2:65][N:66]5[CH2:71][CH2:70][O:69][CH2:68][CH2:67]5)=[CH:30][C:25]=4[S:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 59380394HCID 59380394, compound

Product 1

HCID 59380424HCID 59380424, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)[1]benzothieno[2,3-d]pyrimidin-7-ol (50 mg, 0.11 mmol, from Example 34) in THF (2 mL) was added triphenylphosphine (43.5 mg, 0.17 mmol, 1.5 equiv) and 1,1′-Azobis(N,N-dimethylformamide) (28.6 mg, 0.17 mmol, 1.5 equiv) under nitrogen. The reaction mixture was stirred at rt for 5 mins and 4-(2-hydroxyethyl)morpholine (21.8 mg, 0.17 mmol, 1.5 equiv) was then. The reaction mixture was stirred at rt for 15 h and it was concentrated in vacuo. The crude material was purified by preparative HPLC to give N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-7-(2-morpholin-4-ylethoxy)[1]benzothieno[2,3-d]pyrimidin-4-amine as a white solid (18.1 mg, 29%). 1H-NMR (DMSO-d6) δ 8.08 (broad s, NH), 7.65 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 6.91 (m, 2H), 6.74 (m, 3H), 6.63 (m, 1H), 6.48-6.37 (m, 3H), 4.42 (s, 2H), 3.38 (t, 2H), 2.75 (t, 4H), 1.90 (t, 2H), 1.65 (t, 4H), LCMS RT=2.75 min, [M+H]+=565.20.

Workup

  1. stirringThe reaction mixture was stirred at rt for 15 h
  2. concentrationit was concentrated in vacuo
  3. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-a2dd018010f548fcbcb062a4879a9b44
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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