Imidazole → 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamide

HRID 2172335Notes

Reaction equation

HRID 2172335 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].N1C=CN=C1.[S:12](Cl)(Cl)(=[O:14])=[O:13].Cl.[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1[C:30]1[C:31]2[CH2:39][CH2:38][NH:37][CH2:36][C:32]=2[N:33]=[CH:34][N:35]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[CH:22][C:21]=1[C:30]1[C:31]2[CH2:39][CH2:38][N:37]([S:12]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)(=[O:14])=[O:13])[CH2:36][C:32]=2[N:33]=[CH:34][N:35]=1

Participants

7

Reactant 5

HCID 795ImidazoleHCID 21552-AminothiazoleHCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 898137684-(2-Methoxy-4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride

Product 1

HCID 717373714-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamideYield 60.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of thiazol-2-amine (0.097 g, 0.970 mmol) and imidazole (0.198 g, 2.91 mmol) in 4 mL of DCM was cooled to −78° C. Sulfuryl chloride (0.079 ml, 0.970 mmol) was added, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional 30 minutes. 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride (0.150 g, 0.485 mmol) was added, followed by n,n-diisopropylethylamine (0.847 ml, 4.85 mmol), and the reaction mixture was heated to reflux for one hour, after which time the reaction was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18, 30μ 55 g, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamide (0.138 g, 0.293 mmol, 60.4% yield). 1H NMR (MeCN-d3) δ: 8.96 (s, 1H), 7.33-7.42 (m, 3H), 6.93 (d, J=4.8 Hz, 1H), 6.55 (d, J=4.8 Hz, 1H), 4.35 (br. s., 2H), 3.79-3.87 (m, 3H), 3.08-3.53 (m, 2H), 2.39-2.89 (m, 1H); (M+H)+=472.0.

Workup

  1. customthe cooling bath was removed
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for one hour
  4. concentrationafter which time the reaction was concentrated
  5. customPurification of the crude residue by reverse phase column chromatography [Puriflash C18, 30μ 55 g, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-ab2b68b8f99b4dc2a68f87d7de58f628
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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