Diisopropylethylamine → HCID 178455248, compound

HRID 2169341Notes

Reaction equation

HRID 2169341 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([OH:30])=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[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.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH2:42][CH:43]1[CH2:45][CH2:44]1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(N(CC)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.O>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:42][CH:43]1[CH2:44][CH2:45]1)[C:28]([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([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:29])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].[CH2:1]([O:8][C:9]1[C:10]([C:28]([OH:30])=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:18][CH2:19][CH2:20][CH2:21]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

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 69361897[2-(tert-Butyl-dimethylsilanyloxy)-ethyl]-cyclopropylmethyl-amineHCID 178524866HCID 178524866, compound

Product 1

HCID 178455248HCID 178455248, compoundYield 120.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution mixture of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (283) (250 mg, 0.62 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropylmethyl-amine (8i) (170 mg, 0.74 mmol) in dimethylformamide (3 mL) were added N,N-diisopropylethylamine (0.3 mL, 1.85 mmol) and HATU (352 mg, 0.93 mmol). The reaction mixture was stirred at room temperature for 20 h. Water (75 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic part was washed with water (3×50 mL) and brine (2×30 mL) and dried and concentrated. The crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropylmethyl-amide (304) (380 mg, 99.82%) as a light yellow sticky solid.

Workup

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

Sources & evidence

ORD record
ord-8e6774761eef461ca42baee03f28b614
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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