Ammonia → HCID 178457361, compound

HRID 2040713Notes

Reaction equation

HRID 2040713 reaction equation
Cl.[CH:2]1([C:6]2[CH:45]=[CH:44][C:9]3[NH:10][C:11]([CH2:13][CH2:14][CH:15]4[CH2:18][CH:17]([N:19]([CH2:23][C@@H:24]5[C@H:28]6[O:29]C(C)(C)[O:31][C@H:27]6[C@H:26]([N:34]6[CH:42]=[N:41][C:40]7[C:35]6=[N:36][CH:37]=[N:38][C:39]=7[NH2:43])[O:25]5)[CH:20]([CH3:22])[CH3:21])[CH2:16]4)=[N:12][C:8]=3[CH:7]=2)[CH2:5][CH2:4][CH2:3]1.N>CO>[NH2:43][C:39]1[N:38]=[CH:37][N:36]=[C:35]2[C:40]=1[N:41]=[CH:42][N:34]2[C@H:26]1[C@H:27]([OH:31])[C@H:28]([OH:29])[C@@H:24]([CH2:23][N:19]([CH:17]2[CH2:18][CH:15]([CH2:14][CH2:13][C:11]3[NH:10][C:9]4[CH:44]=[CH:45][C:6]([CH:2]5[CH2:5][CH2:4][CH2:3]5)=[CH:7][C:8]=4[N:12]=3)[CH2:16]2)[CH:20]([CH3:22])[CH3:21])[O:25]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 178457359HCID 178457359, compound

Product 1

HCID 178457361HCID 178457361, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

12N HCl (24 mmol, 2 ml) was added dropwise to a solution of 9-[(3aR,4R,6R,6aR)-6-[({3-[2-(5-cyclobutyl-1H-1,3-benzodiazol-2-yl)ethyl]cyclobutyl}(propan-2-yl)amino)methyl]-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine (120 mg, 0.164 mmol) in MeOH (2 ml) at 0° C. whilst stirring. This was then allowed to warm to RT and continued for 6 hours. The reaction mixture was cooled to 0° C. and basified with 7N NH3 in MeOH (10 ml). This was then evaporated in vacuo. The crude product was absorbed onto silica gel (1 ml), placed onto an isolute flash Si cartridge (10 g) and purified, eluting with 7N NH3 in MeOH:DCM (1:9) to give a white solid, 36 mg (38%); MS (ESI+) for C30H40N8O3 m/z 561.45 [M+H]+; HPLC purity 100% (ret. time, 1.13 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 8.29 (d, J=4.6 Hz, 1H), 8.20 (d, J=1.6 Hz, 1H), 7.50-7.18 (m, 2H), 7.06 (ddd, J=8.3, 4.6, 1.3 Hz, 1H), 6.01-5.90 (m, 1H), 4.73 (dd, J=9.8, 5.1 Hz, 1H), 4.26 (q, J=5.4 Hz, 1H), 4.14-4.03 (m, 1H), 3.60-3.15 (m, 2H), 3.07-2.86 (m, 2H), 2.84-2.67 (m, 3H), 2.42-2.31 (m, 2H), 2.25-2.11 (m, 4H), 2.10-1.95 (m, 2H), 1.92-1.74 (m, 4H), 1.57 (dd, J=12.2, 6.2 Hz, 1H), 1.02 (dd, J=6.6, 4.0 Hz, 3H), 0.95 (dd, J=6.6, 2.3 Hz, 3H).

Workup

  1. customThis was then evaporated in vacuo
  2. customThe crude product was absorbed onto silica gel (1 ml)
  3. custompurified
  4. washeluting with 7N NH3 in MeOH:DCM (1:9)
  5. customto give a white solid, 36 mg (38%)
  6. customHPLC purity 100% (ret. time, 1.13 min)

Sources & evidence

ORD record
ord-cedbdb9164204670b360d4bd861449e0
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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