Methylamine → HCID 178485043, compound

HRID 2189952Notes

Reaction equation

HRID 2189952 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]([C:10]([N:12]([O:14][CH3:15])[CH3:13])=[O:11])[N:8]=[C:7]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])[S:6]1.C(N(CC)CC)C.C1C=CC(O[C:44](OC2C=CC=CC=2)=[N:45][C:46]#[N:47])=CC=1.[CH3:55][NH2:56]>CC(O)C.CO>[C:55](/[N:47]=[C:46](/[NH:45][CH3:44])\[NH:1][CH2:2][CH2:3][CH2:4][C:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]([C:10]([N:12]([O:14][CH3:15])[CH3:13])=[O:11])[N:8]=[C:7]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])[S:6]1)#[N:56]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 688090Diphenyl N-CyanocarbonimidateHCID 46189839HCID 46189839, compound

Product 1

HCID 178485043HCID 178485043, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
23 °C

Procedure

2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide (61 mg, 0.145 mmol, prepared as described in WO 2006/044825 Example 121) was weighed into a flask, then dissolved in 2.0 mL IPA. Triethylamine (0.051 ml, 0.362 mmol) was then added, followed by diphenyl cyanocarbonimidate (69 mg, 0.290 mmol). The reaction was stirred at 23° C. for 1.5 hours, then transferred to a pressure tube, followed by addition of 3 mL of methyl amine (2.4 ml, 4.9 mmol) in MeOH. The reaction was then placed in a 60° C. bath for 12 hours and then concentrated. The residue was purified by flash column chromatography (3-7% MeOH/DCM) affording the desired product (27 mg, 37%) as an orange foam film. MS ESI (+) m/z 502 (M+E) detected; 1H NMR (400 MHz, CDCl3) δ 7.52 (m, 1H), 7.46 (d, J=8.0H7-2H), 7.37 (m, 2H), 7.30 (m, 1H), 7.10 (m, 2H), 5.70 (m, 1h), 3.79 (s, 3H), 3.40 (m, 3H), 3.16 (m, 1H), 3.14 (s, 3H), 2.85 (s, 3H), 2.45 (m, 1H), 2.10 (m, 1H).

Workup

  1. customtransferred to a pressure tube
  2. customwas then placed in a 60° C.
  3. customfor 12 hours
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (3-7% MeOH/DCM)

Sources & evidence

ORD record
ord-731733996ef04fe3992c28b9971f6357
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

Loading…