Phenol → 6-(4-chlorophenyl)-3-{4-[2-(3-fluoropyrrolidin-1-yl)ethoxy]-3-methoxyphenyl}thieno[3,2-d]pyrimidin-4(3H)-one

HRID 1181360Notes

Reaction equation

HRID 1181360 reaction equation
[F:1][CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][C:11]=2[O:19][CH3:20])[CH2:3]1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[S:32][C:31]([C:33](OC)=[O:34])=[C:30](/[N:37]=[CH:38]/N(C)C)[CH:29]=2)=[CH:24][CH:23]=1.C1(O)C=CC=CC=1>C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[S:32][C:31]3[C:33](=[O:34])[N:16]([C:13]4[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:4]5[CH2:5][CH2:6][CH:2]([F:1])[CH2:3]5)=[C:11]([O:19][CH3:20])[CH:12]=4)[CH:38]=[N:37][C:30]=3[CH:29]=2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 693735413-Fluoro-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidineHCID 178499302HCID 178499302, compound

Product 1

HCID 101853586-(4-chlorophenyl)-3-{4-[2-(3-fluoropyrrolidin-1-yl)ethoxy]-3-methoxyphenyl}thieno[3,2-d]pyrimidin-4(3H)-oneYield 11.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
200 °C

Procedure

3-Fluoro-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidine (0.0442 g, 0.1740 mmol) and methyl 5-(4-chlorophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}thiophene-2-carboxylate (0.056 g, 0.1740 mmol) were charged to a flask. Phenol (1 g) was added and the reaction heated to 200° C. The reaction was stirred for 45 min until all starting material was gone. The mix was then cooled to RT, diluted with CH2Cl2 (30 mL) and washed with 1N NaOH (2×30 mL), water (1×30 mL), brine (1×30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified on a chromatatron (98:2 CH2Cl2:MeOH) to give 0.010 g (0.020 mmol, 11%) of the product as a tan solid. 1H NMR (CDCl3) δ 8.13 (s, 1H), 7.65 (d, 2H, J=8.3 Hz), 7.52 (s, 1H), 7.43 (d, 2H, J=8.4 Hz), 7.00 (d, 1H, J=8.4 Hz), 6.93 (m, 2H), 5.29-5.13 (m,1H), 4.23 (t, 2H, J=5.7 Hz), 3.88 (s, 3H), 3.12-2.93 (m, 5H), 2.68 (bs, 1H), 2.25-2.06 (m, 2H).

Workup

  1. temperatureThe mix was then cooled to RT
  2. washwashed with 1N NaOH (2×30 mL), water (1×30 mL), brine (1×30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on a chromatatron (98:2 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-ad5c54edae6149c9b80d02527d8b2dc4
Source dataset
uspto-grants-2007_10
Patent number
US07285557B2

Reaction notes

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