Diisopropylethylamine → HCID 57495362, compound

HRID 242346Notes

Reaction equation

HRID 242346 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.Cl.[CH3:44][O:45][C:46]1[N:51]=[CH:50][C:49]([N:52]2[CH2:67][CH2:66][C:55]3[N:56]=[CH:57][N:58]=[C:59]([O:60][C@H:61]4[CH2:65][CH2:64][NH:63][CH2:62]4)[C:54]=3[CH2:53]2)=[CH:48][C:47]=1[C:68]([F:71])([F:70])[F:69]>CN(C=O)C>[CH3:44][O:45][C:46]1[N:51]=[CH:50][C:49]([N:52]2[CH2:67][CH2:66][C:55]3[N:56]=[CH:57][N:58]=[C:59]([O:60][C@H:61]4[CH2:65][CH2:64][N:63]([C:6]([C:4]5[N:3]=[CH:2][O:1][CH:5]=5)=[O:8])[CH2:62]4)[C:54]=3[CH2:53]2)=[CH:48][C:47]=1[C:68]([F:71])([F:69])[F:70]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 142814301,3-Oxazole-4-carboxylic acidHCID 57495351HCID 57495351, compound

Product 1

HCID 57495362HCID 57495362, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the oxazole-4-carboxylic acid (27 mg, 0.24 mmol)) and HBTU (89 mg, 0.24 mmol) in DMF (1 mL) was added N,N-diisopropylethylamine (0.08 mL, 0.45 mmol). The mixture was stirred for 20 min and then 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine dihydrochloride (100 mg, 0.214 mmol) and additional N,N-diisopropylethylamine (0.08 mL, 0.45 mmol) were added. The mixture was allowed to stir at room temperature for 30 min. Purified by reverse phase Gilson HPLC (Method A) and subsequent neutralization of the combined fractions over PL-HCO3 MP to give {(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-oxazol-4-yl-methanone as a yellow solid (38 mg, 36% yield) 1H NMR (400 MHz, DMSO-d6, 298K) δ ppm 2.11-2.39 (m, 2 H) 2.80-3.01 (m, 2 H) 3.22-4.29 (m, 11 H) 5.59-5.80 (m, 1 H) 7.72-7.94 (m, 1 H) 8.10-8.29 (m, 1 H) 8.41-8.55 (m, 1 H) 8.57-8.77 (m, 2 H) LCMS: [M+H]+=491.1, Rt(1)=1.69 min.

Workup

  1. stirringto stir at room temperature for 30 min
  2. customPurified by reverse phase Gilson HPLC (Method A) and subsequent neutralization of the combined fractions over PL-HCO3 MP

Sources & evidence

ORD record
ord-355762b2cb704fb8a3460adbf364e84e
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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