Triethylamine → HCID 9795791, compound

HRID 1417017Notes

Reaction equation

HRID 1417017 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH:9][CH:10]=[O:11])=[C:4](Cl)[N:3]=1.[NH2:13][C@@H:14]1[CH2:18][C@H:17]([CH2:19][OH:20])[CH:16]=[CH:15]1.C(N(CC)CC)C>C(O)C>[NH2:1][C:2]1[N:3]=[C:4]([NH:13][C@@H:14]2[CH2:18][C@H:17]([CH2:19][OH:20])[CH:16]=[CH:15]2)[C:5]([NH:9][CH:10]=[O:11])=[C:6]([Cl:8])[N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9793729(1S,4R)-4-amino-2-cyclopentene-1-methanolHCID 10198177N-(2-Amino-4,6-dichloropyrimidin-5-yl)formamide

Product 1

HCID 9795791HCID 9795791, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

N-(2-Amino-4,6-dichloro-5-pyrimidinyl)formamide (Example 3, 2.07 g, 10.0 mmol) was stirred in refluxing absolute ethanol (40 mL) under nitrogen to achieve partial dissolution. To this stirred mixture was added a solution of freshly prepared (1S,4R)-4-amino-2-cyclopentene-1-methanol (PCT Application 9204015.3, 1.57 g, 12.5 mmol as 90%) in ethanol (15 mL) followed by triethylamine (3.5 mL, 25 mmol, freshly distilled from calcium hydride). After 14 hours of reflux, the resulting dark solution was cooled and 1N sodium hydroxide (10 mL) was added. The volatiles were evaporated in vacuo. The residual tan solid foam was dissolved in 5% methanol-ethyl acectate, and the solution was washed through a silica gel pad to give the title compound as an off-white solid (2.50 g, 88%), after evaporation of solvents. Recrystallization of the solid from ethyl acetate-methanol (20:1) gave the title compound (VIa) as fine white crystals (2.29 g, 81%), m.p. 177-178° C.; mass spectrum (CI/CH4): 286, 284 (M+1), 190, 188 (B+H); 1H-NMR (DMSO-d6)δ: 8.99 and 8.58 (s and d, J=11.1 Hz, total 1, amide NH), 8.11 and 7.80 (s and d, J=11.1 Hz, total 1, amide CH), 6.77 and 6.61 (two d, J=8.0 Hz) overlapping 6.60 and 6.48 (two br s, total 3, NH and NH2), 5.85 and 5.70 (two m, 1 each, CH=CH), 5.15-5.00 (m, 1, NCH), 4.71 (t, J=5.1, 1, OH), 3.45-3.30 (m overlapping H2O, OCH2), 2.80~2.65 (m, 1, CH), 2.45-2.25 and 1.45-1.30 (both m, 1 each, CH2); [α]20 589 +21.2°, [α]20 578 +22.2°, [α]20 546 +25.2°, [α]20 436 +41.4°, [α]20 365 +48.3° (c 0.50, methanol).

Workup

  1. dissolutiondissolution
  2. distillationfreshly distilled from calcium hydride)
  3. temperatureAfter 14 hours of reflux
  4. temperaturethe resulting dark solution was cooled
  5. addition1N sodium hydroxide (10 mL) was added
  6. customThe volatiles were evaporated in vacuo
  7. dissolutionThe residual tan solid foam was dissolved in 5% methanol-ethyl acectate
  8. washthe solution was washed through a silica gel pad

Sources & evidence

ORD record
ord-d9b57534b2a3472e8a06c0101b6cad2f
Source dataset
uspto-grants-1999_06
Patent number
US05917042

Reaction notes

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