Pyridine → Sufugolix

HRID 23255Notes

Reaction equation

HRID 23255 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:33][C:11]3[N:12]([CH2:24][C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[C:13](=[O:23])[N:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15](=[O:16])[C:10]=3[C:9]=2[CH2:34][N:35]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH3:36])=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl.[CH3:51][O:52][NH2:53].C(N(CC)CC)C.C[C:62](N(C)C)=[O:63]>O>[CH2:37]([N:35]([CH2:34][C:9]1[C:10]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:13](=[O:23])[N:12]([CH2:24][C:25]3[C:26]([F:32])=[CH:27][CH:28]=[CH:29][C:30]=3[F:31])[C:11]=2[S:33][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:62]([NH:53][O:52][CH3:51])=[O:63])=[CH:7][CH:6]=1)[CH3:36])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 31374DimethylacetamideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 109190521-(2,6-difluorobenzyl)-6-(4-aminophenyl)-5-((benzyl(methyl)amino)methyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 3038517SufugolixYield 98.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione (0.50 g, 0.84 mmol) was dissolved in dimethyl acetamide (2 ml), pyridine (82 μl, 1.01 mmol) was added thereto, and the mixture was stirred. Phenyl chloroformate (phenyl chlorocarbonate)(126 μl, 1.01 mmol) was added thereto dropwise under ice-cooling, and the mixture was stirred at room temperature for 2 hours. O-methylhydroxylamine hydrochloride (77.2 mg, 92.4 μmol) and triethylamine (336 μl, 2.77 mmol) were added thereto, and the mixture was stirred at 50° C. for 12 hours. Water (30 ml) was added thereto, and the mixture was vigorously stirred. The crystals were filtered, and dried under vacuum at 40° C. to give white crystals of 5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-6-[4-(3-methoxyureido)phenyl]-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione (0.55 g, 98.2%).

Workup

  1. temperaturedropwise under ice-cooling
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. stirringthe mixture was stirred at 50° C. for 12 hours
  4. stirringthe mixture was vigorously stirred
  5. filtrationThe crystals were filtered
  6. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-ee84b7cd54354a95a48086fd0327be91
Source dataset
uspto-grants-2005_02
Patent number
US06849738B2

Reaction notes

Loading…