Diisopropylethylamine → tert-butyl N-[(1R)-1-methyl-1-[[6-(3-methylchroman-5-yl)oxy-3-pyridyl]carbamoyl]propyl]carbamate

HRID 527609Notes

Reaction equation

HRID 527609 reaction equation
[CH3:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:12][C:13]2[N:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[O:4][CH2:3]1.[C:20]([O:24][C:25]([NH:27][C@:28]([CH3:34])([CH2:32][CH3:33])[C:29](O)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:34][C@:28]([NH:27][C:25](=[O:26])[O:24][C:20]([CH3:23])([CH3:22])[CH3:21])([C:29](=[O:30])[NH:19][C:16]1[CH:17]=[N:18][C:13]([O:12][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[C:10]=2[CH2:11][CH:2]([CH3:1])[CH2:3][O:4]3)=[CH:14][CH:15]=1)[CH2:32][CH3:33]

Participants

6

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 14284791(R)-2-((tert-Butoxycarbonyl)amino)-2-methylbutanoic acidHCID 679585226-[(3-methyl-3,4-dihydro-2H-chromen-5-yl)oxy]-3-pyridinamine2×

Product 1

HCID 86698444tert-butyl N-[(1R)-1-methyl-1-[[6-(3-methylchroman-5-yl)oxy-3-pyridyl]carbamoyl]propyl]carbamateYield 401.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 8 mL 6-[(3-methyl-3,4-dihydro-2H-chromen-5-yl)oxy]-3-pyridinamine (Intermediate 119, 82.4 mg, 0.0305 mmol), (2R)-2-(tert-butoxycarbonylamino)-2-methyl-butanoic acid (59.7 mg, 0.275 mmol) and DIPEA (0.080 mL, 0.458 mmol) were dissolved in N,N-Dimethylformamide (DMF) (2 mL) to give a pale yellow solution. HATU (151 mg, 0.397 mmol) was added. The reaction mixture was stirred at room temperature over week-end. The reaction mixture was evaporated in vacuo and the residue was purified by flash chromatography on silica gel using a column SNAP 25 g and cyclohexane/ethyl acetate from 3:1 to 1:2 as eluents affording the title compound (55.8 mg) as white solid.

Workup

  1. customto give a pale yellow solution
  2. customThe reaction mixture was evaporated in vacuo
  3. customthe residue was purified by flash chromatography on silica gel using a column SNAP 25 g and cyclohexane/ethyl acetate from 3:1 to 1:2 as eluents

Sources & evidence

ORD record
ord-1ef0df30572c4a219a72925a05809134
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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