Diisopropylethylamine → HCID 178490990, compound

HRID 2200909

Reaction equation

HRID 2200909 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[CH2:5][NH:6][C:7]1[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]([N:16]2[CH2:20][CH2:19][CH2:18][C@H:17]2[CH2:21][OH:22])[N:8]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:61][C@H:62]1[CH2:67][CH2:66][C@H:65]([OH:68])[CH2:64][CH2:63]1>CN(C=O)C.O.C(OCC)(=O)C>[OH:68][C@H:65]1[CH2:66][CH2:67][C@H:62]([NH:61][C:13]([C:12]2[C:7]([NH:6][CH2:5][C:4]3[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:2]([Cl:1])[CH:3]=3)=[N:8][C:9]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH2:21][OH:22])=[N:10][CH:11]=2)=[O:15])[CH2:63][CH2:64]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 671193354-[(3-Chloro-4-methoxybenzyl)amino]-2-[(2S)-2-(hydroxymethyl)-pyrrolidin-1-yl]pyrimidine-5-carboxylic acidHCID 178511715HCID 178511715, compound

Product 1

HCID 178490990HCID 178490990, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In DMF (20 mL) was dissolved (s)-4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)tetrahydropyrrole-1-yl)-5-pyrimidine carboxylic acid (3.9 g, 10 mmol). The solution was cooled in an ice bath. HATU (5.67 g, 15 mmol) and DIPEA (1.93 g, 15 mmol) were added. After 20 min, trans-4-aminocyclohexanol (1.39 g, 12 mmol) was added in batches. The reaction was conducted overnight. LC-MS was used to monitor the reaction. Ethyl acetate (50 mL) and water (50 mL) were added. The separate aqueous phase was washed with ethyl acetate twice. The organic phase was combined, dried, concentrated and purified by silica gel column chromatography (VDCM:VMeOH=15:1) to give the product (1.5 g, 31% yield).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. waitThe reaction was conducted overnight
  3. customthe reaction
  4. washThe separate aqueous phase was washed with ethyl acetate twice
  5. customdried
  6. concentrationconcentrated
  7. custompurified by silica gel column chromatography (VDCM:VMeOH=15:1)

Sources & evidence

ORD record
ord-8e0f3bded7454bd69dfe3fd8298ea41a
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Linked notes

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