Diisopropylethylamine → HCID 178484774, compound

HRID 2169436Notes

Reaction equation

HRID 2169436 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:31](O)=[O:32])=[N:11][C:12]([CH2:16][C:17]2([N:22]3[C:26]4=[N:27][CH:28]=[CH:29][CH:30]=[C:25]4[CH:24]=[CH:23]3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[Si:43]([O:50][CH2:51][CH2:52][NH:53][CH3:54])([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O.C(OCC)(=O)C>[Si:43]([O:50][CH2:51][CH2:52][N:53]([CH3:54])[C:31]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([N:22]3[C:26]4=[N:27][CH:28]=[CH:29][CH:30]=[C:25]4[CH:24]=[CH:23]3)[CH2:18][CH2:19][CH2:20][CH2:21]2)[N:11]=1)=[O:32])([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:44])[CH3:45]

Participants

8

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 16203640N-(2-(tert-Butyldimethylsilyloxy)ethyl)methylamineHCID 178524881HCID 178524881, compound

Product 1

HCID 178484774HCID 178484774, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-pyrrolo[2,3-b]pyridin-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (404) (250 mg, 0.56 mmol) in dimethylformamide (5 mL) was added N,N-diisopropylethylamine (0.3 mL, 1.69 mmol) followed by [2-(tert-butyl-dimethylsilanyloxy)-ethyl]methyl-amine (8a) (320 mg, 1.69 mmol) and HATU (320 mg, 0.84 mmol) and stirring was continued for 1 h (TLC, ethyl acetate, Rf=0.5). Water (30 mL) was added and the mixture was extracted with ethyl acetate (2×20 mL). The organic part was washed with water (2×100 mL) and brine (2×50 mL). The organic phase was thereafter dried and concentrated. The crude product was purified by Combi-Flash column (eluted at 30-40% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-pyrrolo[2,3-b]pyridin-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amide (405) (300 mg, 87%) as a light yellow sticky solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (2×20 mL)
  2. washThe organic part was washed with water (2×100 mL) and brine (2×50 mL)
  3. customThe organic phase was thereafter dried
  4. concentrationconcentrated
  5. customThe crude product was purified by Combi-Flash column (eluted at 30-40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f35e3eeaeff249808f5d40c8fd36c383
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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