2-Aminopyrimidine-5-carbaldehyde → HCID 56639915, compound

HRID 709415Notes

Reaction equation

HRID 709415 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([C@@H:29]2[CH2:31][C@H:30]2[NH2:32])=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[NH2:33][C:34]1[N:39]=[CH:38][C:37]([CH:40]=O)=[CH:36][N:35]=1.[BH4-].[Na+]>ClCCCl>[CH2:15]([O:22][C:23]1[CH:24]=[CH:25][C:26]([C@@H:29]2[CH2:31][C@H:30]2[NH:32][CH2:40][C:37]2[CH:36]=[N:35][C:34]([NH2:33])=[N:39][CH:38]=2)=[CH:27][CH:28]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 7690972-Aminopyrimidine-5-carbaldehydeHCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 51888238(1R,2S)-2-(4-(Benzyloxy)phenyl)cyclopropan-1-amine2×

Product 1

HCID 56639915HCID 56639915, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxy borohydride (883 mg, 4.166 mmol) was added slowly at 0° C. to a solution of (trans)-2-(4-(benzyloxy)phenyl)cyclopropanamine (Intermediate B, 500 mg, 2.083 mmol), 2-aminopyrimidine-5-carbaldehyde (256 mg, 2.083 mmol) in DCE (10 mL) and stirred for 20 h. After completion, the solvent was evaporated. The residue was dissolved in Methanol (15 mL), NaBH4 (237 mg, 6.249 mmol) was added slowly at 0° C. and stirred for 3 h. After completion, the solvent was evaporated, the residue was dissolved in ice water (20 mL) and extracted with EtOAc (2×20 mL) The combined organic layers were washed with brine (20 mL) and dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by prep HPLC to afford 5-(((trans)-2-(4-(benzyloxy)phenyl)cyclopropylamino)methyl)pyrimidin-2-amine (180 mg, 25%) as white solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 0.85 (q, 1H), 0.90 (quin, 1H), 1.73 (m, 1H), 2.07 (m, 1H), 2.75 (brs, 1H), 3.53 (s, 2H), 5.04 (s, 2H), 6.46 (s, 2H), 6.85 (d, 2H), 6.92 (d, 2H), 7.33 (m, 1H), 7.42 (m, 4H), 8.11 (s, 2H). Mass (M+H): 347.3

Workup

  1. customAfter completion, the solvent was evaporated
  2. dissolutionThe residue was dissolved in Methanol (15 mL)
  3. stirringstirred for 3 h
  4. customAfter completion, the solvent was evaporated
  5. dissolutionthe residue was dissolved in ice water (20 mL)
  6. extractionextracted with EtOAc (2×20 mL) The combined organic layers
  7. washwere washed with brine (20 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude residue was purified by prep HPLC

Sources & evidence

ORD record
ord-90deeaf7b94a43318bda5dad4b3998a2
Source dataset
uspto-grants-2015_11
Patent number
US09181198B2

Reaction notes

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