Acetic Acid → HCID 86695099, compound

HRID 1503922Notes

Reaction equation

HRID 1503922 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:32])[CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:27]3[C:26]4[C@@H:25]([CH2:28][C:29](O)=[O:30])[CH2:24][CH2:23][C:22]=4[S:21][C:20]=3[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.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.Cl.[NH2:71][CH2:72][C:73]([NH:75][CH3:76])=[O:74]>CN(C=O)C.O>[CH3:32][N:8]([CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:27]3[C:26]4[C@@H:25]([CH2:28][C:29](=[O:30])[NH:71][CH2:72][C:73](=[O:74])[NH:75][CH3:76])[CH2:24][CH2:23][C:22]=4[S:21][C:20]=3[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138422022-amino-N-methylacetamide hydrochloride2×HCID 68115387HCID 68115387, compound

Product 1

HCID 86695099HCID 86695099, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

For the preparation of the starting material compound 35.1, please see Example 35. A solution of 2-[(3R)-12-[(4-[[tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acid (150 mg, 0.32 mmol, 1.00 equiv), HATU (183 mg, 0.48 mmol, 1.48 equiv), DIPEA (165 mg) and 2-amino-N-methylacetamide hydrochloride (intermediate 83.5, 120 mg, 0.96 mmol, 3.0 equiv) in 10 mL of anhydrous DMF was stirred for 24 h at room temperature under nitrogen. After completion of the reaction, the resulting solution was diluted with water and extracted with 3×40 mL of ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4) and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (30:1) to afford tert-butyl N-methyl-N-(4-[[(3R)-3-([[(methylcarbamoyl)methyl]carbamoyl]methyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)carbamate (130 mg, 75%) as a yellow oil. MS: m/z 532 [M+H]+.

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with 3×40 mL of ethyl acetate
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7a45004c95ac48c7b3df764e9fd99eb8
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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