Diisopropylethylamine → HCID 178457488, compound

HRID 2169235Notes

Reaction equation

HRID 2169235 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:29](O)=[O:30])=[N:11][C:12]([CH2:16][C:17]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:32]([O:39][CH2:40][CH2:41][NH:42][CH:43]([CH3:45])[CH3:44])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].C(N(CC)C(C)C)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C)C=O.ClCCl.O.CO>[Si:32]([O:39][CH2:40][CH2:41][N:42]([CH:43]([CH3:45])[CH3:44])[C:29]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:21][CH:20]=[CH:19][N:18]=2)[N:11]=1)=[O:30])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178524882HCID 178524882, compound

Product 1

HCID 178457488HCID 178457488, compoundYield 36.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(3-phenyl-pyridin-2-ylmethyl)-pyrimidine-4-carboxylic acid (164) (370 mg, 0.89 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (292 mg, 1.34 mmol) in dimethylformamide (5 mL) was added N,N-diisopropylethylamine (0.5 mL, 2.69 mmol), the mixture was cooled to 0° C., T3P (50 wt % in ethyl acetate) (1.8 g, 2.69 mmol) was added, and the mixture was stirred for 16 h at room temperature. Silica thin layer chromatography was performed (5% methanol in dichloromethane, Rf=0.3). Water (100 mL) was added, the mixture was extracted with ethyl acetate, dried and concentrated, and purified by a CombiFlash column (eluted at 2-5% methanol in dichloromethane) to get 5-benzyloxy-6-hydroxy-2-(3-phenyl-pyridin-2-ylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (165) (200 mg, 36.46%) as a yellow sticky product.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. customdried
  3. concentrationconcentrated
  4. custompurified by a CombiFlash column (eluted at 2-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bd3f7c3142ec4782b152af7ac9d6430c
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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