HCID 67775001, compound → HCID 178494914, compound

HRID 2040721Notes

Reaction equation

HRID 2040721 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:45])[CH:23]2[CH2:26][CH:25]([CH2:27][CH2:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([CH3:43])([CH3:42])[CH2:39][O:40][CH3:41])=[CH:34][C:33]=3[NH2:44])=O)[CH2:24]2)[O:12]1>CC(O)=O>[CH3:41][O:40][CH2:39][C:38]([C:35]1[CH:36]=[CH:37][C:32]2[NH:31][C:29]([CH2:28][CH2:27][CH:25]3[CH2:24][CH:23]([N:22]([CH2:21][C@@H:13]4[C@H:14]5[O:18][C:17]([CH3:19])([CH3:20])[O:16][C@H:15]5[C@H:11]([N:6]5[CH:5]=[N:4][C:3]6[C:7]5=[N:8][CH:9]=[N:10][C:2]=6[NH2:1])[O:12]4)[CH3:45])[CH2:26]3)=[N:44][C:33]=2[CH:34]=1)([CH3:42])[CH3:43]

Participants

3

Reactant 1

HCID 67775001HCID 67775001, compound

Product 1

HCID 178494914HCID 178494914, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

3-[3-({[(3aR,4R,6R,6aR)-6-(6-Amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]methyl}(methyl)amino)cyclobutyl]-N-[2-amino-4-(1-methoxy-2-methylpropan-2-yl)phenyl]propanamide (1.036 g, 1.66 mmol) was dissolved in AcOH (17 ml) and heated to 50° C. for 5 h. The reaction was concentrated in vacuo and the residue was dissolved in DCM (75 ml) and sat. NaHCO3 solution (75 ml) was added. The organic layer was separated and the aqueous layer was extracted with DCM (2×75 nil). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give the crude product as a dark orange oil (0.850 g, 94%). The product was purified using neutral prep-HPLC to give the product as a pale yellow oil (0.485 g, 47%, 88% pure): MS (ESI+) for C32H44N8O4 m/z 605.4 [M+H]+; LC purity 88% (ret. time, 1.25 min); 1HNMR (500 MHz, CDCl3) δH 10.44 (dd, J=207.7, 22.9 Hz, 1H), 8.41 (d, J=17.1 Hz, 1H), 8.16 (d, J=13.8 Hz, 1H), 7.89-7.58 (m, 1H), 7.54-7.29 (m, 2H), 6.15 (d, J=10.9 Hz, 1H), 5.92-5.56 (m, 3H), 4.98 (d, J=12.5 Hz, 1H), 4.76-4.39 (m, 1H), 3.47 (d, J=6.2 Hz, 2H), 3.33 (d, J=4.8 Hz, 3H), 2.98-2.43 (m, 4H), 2.42-2.00 (m, 6H), 1.99-1.88 (m, 2H), 1.77-1.66 (m, 1H), 1.64 (s, 3H), 1.61-1.48 (m, 1H), 1.44 (d, J=8.1 Hz, 3H), 1.40 (d, J=7.9 Hz, 6H), 1.28 (dd, J=16.0, 9.0 Hz, 1H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue was dissolved in DCM (75 ml)
  3. additionsat. NaHCO3 solution (75 ml) was added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with DCM (2×75 nil)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product as a dark orange oil (0.850 g, 94%)
  10. customThe product was purified

Sources & evidence

ORD record
ord-2b0b47c0dfaf48e494c32946cd4542df
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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