4-Methylmorpholine → HCID 86660771, compound

HRID 2200963Notes

Reaction equation

HRID 2200963 reaction equation
[NH:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2][C:3]([OH:5])=O.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:29][C:30]1[N:59]=[C:33]2[N:34]([C:49]3[CH:54]=[CH:53][CH:52]=[C:51]([C:55]([F:58])([F:57])[F:56])[CH:50]=3)[C:35]([CH3:48])=[C:36]([C:46]#[N:47])[C@@H:37]([C:38]3[CH:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=3)[N:32]2[N:31]=1>C1COCC1>[C:46]([C:36]1[C@@H:37]([C:38]2[CH:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=2)[N:32]2[N:31]=[C:30]([NH:29][C:3](=[O:5])[CH2:2][NH:1][C:6](=[O:7])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[N:59]=[C:33]2[N:34]([C:49]2[CH:54]=[CH:53][CH:52]=[C:51]([C:55]([F:57])([F:56])[F:58])[CH:50]=2)[C:35]=1[CH3:48])#[N:47]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine3×HCID 62365Isobutyl chloroformate2×HCID 78288N-(tert-butoxycarbonyl)glycine2×HCID 66627899(7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride

Product 1

HCID 86660771HCID 86660771, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an atmosphere of argon protective gas, N-Boc-Gly-OH (5 mg, 28 μmol) and NMM (5.3 mg, 52 μmol, 2.4 eq.) were dissolved in abs. THF (1 ml), and isobutyl chloroformate (4.2 mg, 31 μmol, 1.4 eq.) was added at −15° C. (solution A). At −78° C., (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride (10 mg, 22 μmol) and NMM (2.2 mg, 22 μmol, 1 eq.) were added, and the mixture was stirred overnight, during which time it slowly warmed to RT. Since the conversion was still incomplete, more solution A consisting of in each case 285 μmol of N-Boc-Gly-OH, isobutyl chloroformate and NMM in abs. THF was added at −15° C., and the mixture was stirred for 3 d, warming to RT. The reaction mixture was then directly purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (6.3 mg, 50% of theory).

Workup

  1. stirringthe mixture was stirred for 3 d
  2. temperaturewarming to RT
  3. customThe reaction mixture was then directly purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
  4. customAfter lyophilization, the product was obtained as a solid (6.3 mg, 50% of theory)

Sources & evidence

ORD record
ord-131307d5ed6e47579c05278a3205be81
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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