Methanol → (R)-1-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)pyrrolidine-2-carboxylic acid

HRID 2207101Notes

Reaction equation

HRID 2207101 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[C:5]([CH2:16][C:17]2[CH:35]=[CH:34][C:20]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@@H:23]3[C:27]([O:29]C(C)(C)C)=[O:28])=[CH:19][C:18]=2[O:36][CH3:37])=[C:4]([CH3:38])[N:3]=1.FC(F)(F)C(O)=O.CO>C(Cl)(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[C:5]([CH2:16][C:17]2[CH:35]=[CH:34][C:20]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@@H:23]3[C:27]([OH:29])=[O:28])=[CH:19][C:18]=2[O:36][CH3:37])=[C:4]([CH3:38])[N:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 117992865(R)-tert-butyl 1-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)pyrrolidine-2-carboxylate

Product 1

HCID 72549259(R)-1-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)pyrrolidine-2-carboxylic acidYield 79.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the product of step (ii) (70 mg) in chloroform (1.5 mL) was added trifluoroacetic acid (1.5 mL) and the mixture was stirred at RT. After 12 h, methanol (10 mL) was stirred at room temperature. After 12 h, the mixture was concentrated under reduced pressure. 10% aqueous potassium dicarbonate was added and the resulting mixture was extracted with chloroform/EtOH (3/1). The combined organic layer was dried and concentrated under reduced pressure to afford the sub-title compound (50 mg) as a white solid; 1H NMR (methanol-d4); 7.23 (1H, d), 7.02-6.97 (2H, m), 4.47 (1H, m), 4.34 (2H, s), 3.97 (3H, s), 3.85-3.80 (3H, m), 3.64 (1H, m), 3.45-3.41 (2H, m), 2.44 (1H, m), 2.28 (3H, s), 2.11 (2H, m), 1.96 (1H, m), 1.74-1.20 (7H, m), 0.87 (3H, t); LC-MS: m/z 472.

Workup

  1. waitAfter 12 h
  2. concentrationthe mixture was concentrated under reduced pressure
  3. addition10% aqueous potassium dicarbonate was added
  4. extractionthe resulting mixture was extracted with chloroform/EtOH (3/1)
  5. customThe combined organic layer was dried
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2c560ca84cc74c169294a1b76d23bd3c
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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