N,O-Dimethylhydroxylamine → 2-Isopropylamino-6-methyl-pyrimidine-4-carboxylic acid methoxy-methyl-amide

HRID 2069467Notes

Reaction equation

HRID 2069467 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[C:7]([CH3:14])[N:6]=1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN([C:27]([O:31][N:32]1N=NC2C=CC=C[C:33]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CNOC>C(Cl)Cl>[CH3:27][O:31][N:32]([CH3:33])[C:11]([C:9]1[CH:8]=[C:7]([CH3:14])[N:6]=[C:5]([NH:4][CH:1]([CH3:2])[CH3:3])[N:10]=1)=[O:13]

Participants

6

Reactant 4

HCID 14232N,O-DimethylhydroxylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669337152-(Isopropylamino)-6-methylpyrimidine-4-carboxylic acid

Product 1

HCID 866453112-Isopropylamino-6-methyl-pyrimidine-4-carboxylic acid methoxy-methyl-amideYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-isopropylamino-6-methyl-pyrimidine-4-carboxylic acid (2.0 g, 10.2 mmol) in DCM (45 mL), DIPEA (8.8 mL, 51.2 mmol) followed by TBTU (3.9 g, 12.3 mmol) is added. The mixture is stirred at rt for 30 min before N,O-dimethylhydroxylamine (1.20 g, 12.3 mmol) is added. The mixture is stirred at rt for 18 h before it is diluted with DCM, washed with sat. aq. NaHCO3, followed by water, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 1:2 to give 2-isopropylamino-6-methyl-pyrimidine-4-carboxylic acid methoxy-methyl-amide (2.39 g) as a yellow oil; LC-MS: tR=0.66 min, [M+H]+=239.03; 1H NMR (D6-DMSO): δ 1.14 (d, J=6.5 Hz, 6H), 2.28 (s, 3H), 3.23 (s, 3H), 3.67 (s, 3H), 4.05 (m, 1H), 6.50 (s br, 1H), 7.12 (s br, 1H).

Workup

  1. additionis added
  2. additionis added
  3. washwashed with sat. aq. NaHCO3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by CC on silica gel eluting with heptane:EA 1:2

Sources & evidence

ORD record
ord-026240c4ae69424b99e69041d31afc53
Source dataset
uspto-grants-2012_10
Patent number
US08299086B2

Reaction notes

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