1,2-Dichloroethane → 4-benzyloxy-N-[2,2-diethoxy-2-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamide

HRID 2069470Notes

Reaction equation

HRID 2069470 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][C:10]=1[CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.Cl.[NH2:46][CH2:47][C:48]([C:55]1[CH:60]=[C:59]([CH3:61])[N:58]=[C:57]([NH:62][CH:63]([CH3:65])[CH3:64])[N:56]=1)([O:52][CH2:53][CH3:54])[O:49][CH2:50][CH3:51]>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[CH:16][C:12]([C:13]([NH:46][CH2:47][C:48]([O:52][CH2:53][CH3:54])([O:49][CH2:50][CH3:51])[C:55]2[CH:60]=[C:59]([CH3:61])[N:58]=[C:57]([NH:62][CH:63]([CH3:64])[CH3:65])[N:56]=2)=[O:15])=[CH:11][C:10]=1[CH2:19][CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 594979194-Benzyloxy-3-ethyl-5-methyl-benzoic acidHCID 68505990[4-(2-Amino-1,1-diethoxy-ethyl)-6-methyl-pyrimidin-2-yl]-isopropyl-amine dihydrochloride

Product 1

HCID 685084724-benzyloxy-N-[2,2-diethoxy-2-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamideYield 78.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-benzyloxy-3-ethyl-5-methyl-benzoic acid (224 mg, 0.83 mmol) in DMF (5 mL), EDC (175 mg, 0.91 mmol) and HOBt (124 mg, 0.91 mmol) are added. The mixture is stirred at rt for 15 min before DIPEA (0.57 mL, 3.3 mmol) and a solution of crude [4-(2-amino-1,1-diethoxy-ethyl)-6-methyl-pyrimidin-2-yl]-isopropyl-amine dihydrochloride (174 mg, 0.83 mmol) in DMF (2.0 mL) is added. The mixture is stirred at rt for 4 h, diluted with EtOAc (30 mL), and washed with sat. aq. NaHCO3 (15 mL) and brine (15 mL). The org. extract is dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC plates with Heptane/EtOAc 1:1 to give 4-benzyloxy-N-[2,2-diethoxy-2-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-ethyl]-3-ethyl-5-methyl-benzamide (348 mg) as a yellow oil; LC-MS: tR=1.02 min, [M+H]+=535.22.

Workup

  1. washwashed with sat. aq. NaHCO3 (15 mL) and brine (15 mL)
  2. extractionextract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-0717560d4c1044bda090b7de2fec17fb
Source dataset
uspto-grants-2012_10
Patent number
US08299086B2

Reaction notes

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