Methylamine → 5-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}-N-methylnicotinamide

HRID 2102380Notes

Reaction equation

HRID 2102380 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:23]=[N:24][CH:25]=[C:26]([CH:31]=4)[C:27](OC)=[O:28])=[N:14][CH:13]=[N:12][C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:32][NH2:33]>C(O)CCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:23]=[N:24][CH:25]=[C:26]([CH:31]=4)[C:27]([NH:33][CH3:32])=[O:28])=[N:14][CH:13]=[N:12][C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 11647803Methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinate

Product 1

HCID 578030015-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}-N-methylnicotinamideYield 20%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

Methyl 5-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}nicotinate (0.010 g, 0.023 mmol) and methylamine (0.124 g, 0.004 mol) were mixed in 1-butanol (2.00 mL) and the resulting mixture subjected to microwave radiation for 2000 seconds at 170° C., followed by irradiation for 4000 seconds at 180° C. The solvent was removed by evaporation, and the product purified by preparative HPLC to give 2 mg (20%) 5-{4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy}-N-methylnicotinamide hydroformate as a white solid. MS [M+H]=437.1, LC/MS (EI) tR 3.55 min (Method D), 1H NMR (10% MeOD/CDCl3) δ (ppm) 8.93 (s, 1H), 8.43 (s, 1H), 8.20 (s, 1H), 7.70 (s, 1H), 7.60 (s, 1H), 7.40-7.28 (m, 4H), 7.11 (t, J=8.7 Hz, 2H), 3.84 (t, J=6.0 Hz, 2H), 2.95 (d, J=3.6 Hz, 3H), 2.67 (t, J=7.2 Hz, 2H), 1.75-1.59 (m, 2H), 1.59-1.45 (m, 2H)

Workup

  1. customfor 2000 seconds
  2. customat 170° C.
  3. customfollowed by irradiation for 4000 seconds at 180° C
  4. customThe solvent was removed by evaporation
  5. customthe product purified by preparative HPLC

Sources & evidence

ORD record
ord-9adfdbd262e7461ca5d2dbae9590cd4d
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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