Triethylamine → HCID 178496745, compound

HRID 2189934Notes

Reaction equation

HRID 2189934 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](=[O:15])[C@@H:11]([O:13][CH3:14])[CH3:12])[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.[ClH:30].[C:31](=[NH:35])(OC)[CH3:32].C(N(CC)CC)C>CO>[ClH:30].[F:23][C:17]1[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=1[C:7]1[S:6][C@@:5]([CH2:4][CH2:3][CH2:2][NH:1][C:31](=[NH:35])[CH3:32])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]([C:10](=[O:15])[C@@H:11]([O:13][CH3:14])[CH3:12])[N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10313100Ethanimidic acid, methyl ester, hydrochloride (1:1)HCID 60139827HCID 60139827, compound

Product 1

HCID 178496745HCID 178496745, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-1-((S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methoxypropan-1-one (Example 5, Steps A-F; 57.5 mg, 0.117 mmol) and methyl acetimidate hydrochloride (192 mg, 1.75 mmol) in methanol was added triethylamine (355 mg, 3.51 mmol). After heating at 50° C. for 16 hours, the mixture was concentrated under reduced pressure. The residue was chromatographed (15:85:1 MeOH/dichloromethane/NH4OH), and the isolated material %% as treated with excess HCl in MeOH then concentrated to afford the product. MS ESI (+) m/z 461 (M+1) detected. 1H NMR (400 MHz, CD3OD) δ 7.65-7.60 (m, 1H), 7.49-7.45 (m, 2H), 7.42-7.38 (m, 2H), 7.35-7.29 (m, 3H), 4.80 (q, 1H, J=7.1 Hz), 3.50-3.40 (m, 2H), 3.36 (s, 3H), 3.28-3.19 (m, 1H), 2.65-2.57 (m, 1H), 2.22 (s, 3H), 2.21-2.12 (m, 1H), 1.75-1.64 (m, 1H), 1.44 (d, 3H, J=7.1 Hz).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was chromatographed (15:85:1 MeOH/dichloromethane/NH4OH)
  3. additionthe isolated material %% as treated with excess HCl in MeOH
  4. concentrationthen concentrated
  5. customto afford the product

Sources & evidence

ORD record
ord-065d5f7d2bd04b3a83aaa9ede3a2acfd
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

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