Sodium Acetate → tert-Butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-4-(1-methyl-1H-pyrazol-4-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate

HRID 515980Notes

Reaction equation

HRID 515980 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH:22]=O)[C:19]([C:24](OC)=[O:25])=[C:18]([C:28]2[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:34][O:35][C:36]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:37]=1[CH2:44][NH2:45].C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[CH3:34][O:35][C:36]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:37]=1[CH2:44][N:45]1[C:24](=[O:25])[C:19]2[C:18]([C:28]3[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=3)=[N:17][C:16]([NH:15][C@@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[N:21][C:20]=2[CH2:22]1

Participants

7

Reactant 4

HCID 517045Sodium AcetateHCID 5972502,4-DimethoxybenzylamineHCID 5003444Sodium cyanoborohydrideHCID 86654705Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-formyl-6-(1-methyl-1H-pyrazol-4-yl)pyrimidine-5-carboxylate

Product 1

HCID 86654704tert-Butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-4-(1-methyl-1H-pyrazol-4-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamateYield 3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-formyl-6-(1-methyl-1H-pyrazol-4-yl)pyrimidine-5-carboxylate (0.175 g, 0.382 mmol) was dissolved in DCM (2 mL) and MeOH (1 mL). To this mixture was added (2,4-dimethoxyphenyl)methanamine (0.057 mL, 0.382 mmol) and sodium acetate (0.094 g, 1.145 mmol). The mixture was stirred in a capped 20 mL vial for 1 h, after which sodium cyanoborohydride (0.060 g, 0.954 mmol) was added. The reaction mixture was stirred at RT overnight. After the solvent was removed under reduced pressure, the residue was dissolved in DMSO/MeOH (1/1) solution. An off-white solid precipitate was initially formed, which was isolated by vacuum filtration, rinsed with MeOH, and air dried to give a first batch of the title compound (6.7 mg). The mother liquor was purified via preparative HPLC. The fractions were concentrated under reduced pressure until an off-white solid precipitate was formed, which was collected by vacuum filtration and air dried to give a second batch (46 mg) of the title compound (total 62.5 mg, 28%). [M+H] calc'd for C30H39N7O5, 578; found, 578.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. customAfter the solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in DMSO/MeOH (1/1) solution
  4. customAn off-white solid precipitate was initially formed
  5. customwhich was isolated by vacuum filtration
  6. washrinsed with MeOH, and air
  7. customdried

Sources & evidence

ORD record
ord-ea5971c03dc641bfb9ae5430c08b6da9
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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