Water → HCID 178457185, compound

HRID 1054534Notes

Reaction equation

HRID 1054534 reaction equation
C(O)(C(F)(F)F)=O.O.[C:9]([C:13]1[CH:50]=[CH:49][C:16]2[NH:17][C:18]([CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:28][CH:29]3[C@H:33]4[O:34]C(C)(C)[O:36][C@H:32]4[C@H:31]([N:39]4[C:43]5[N:44]=[CH:45][N:46]=[C:47]([NH2:48])[C:42]=5[CH:41]=[CH:40]4)[CH2:30]3)[CH:25]([CH3:27])[CH3:26])=[N:19][C:15]=2[CH:14]=1)([CH3:12])([CH3:11])[CH3:10]>C(Cl)Cl>[NH2:48][C:47]1[C:42]2[CH:41]=[CH:40][N:39]([C@@H:31]3[CH2:30][CH:29]([CH2:28][N:24]([CH2:23][CH2:22][CH2:21][CH2:20][C:18]4[NH:17][C:16]5[CH:49]=[CH:50][C:13]([C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:14][C:15]=5[N:19]=4)[CH:25]([CH3:27])[CH3:26])[C@@H:33]([OH:34])[C@H:32]3[OH:36])[C:43]=2[N:44]=[CH:45][N:46]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 178457184HCID 178457184, compound

Product 1

HCID 178457185HCID 178457185, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

TFA (0.75 ml) followed by water (0.1 ml) was added to a solution of 7-[(3aS,4R,6aR)-6-({[4-(5-tert-butyl-1H-1,3-benzodiazol-2-yl)butyl](propan-2-yl)amino}methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine in DCM (1.5 ml) and stirred at 50° C. for 2 hours. The reaction mixture was then evaporated in vacuo. MeOH (2 ml) was added to the residue and cooled to 0° C. This was basified with 7N ammonia in MeOH (3 ml) and then evaporated to dryness. The product was filtered though a short silica gel column, eluting with 7N ammonia in MeOH:DCM (5/95-1/9). This gave separation of two products plus a mixture of both. The mixed fractions were combined and purified on a prep. TLC plate, eluting twice with 7N ammonia in MeOH:DCM (1:9) to give a white solid (39 mg, 56%); MS (ESI+) for C30H43N7O2. m/z 534.48 [M+H]+; HPLC purity 98% (ret. time, 4.68 min); 1H NMR (250 MHz, MeOD) δ ppm 8.05 (1H, s), 7.48 (1H, s), 7.34-7.43 (1H, m), 7.22-7.31 (1H, m), 7.17 (1H, d, J=3.50 Hz), 6.59 (1H, d, J=3.50 Hz), 4.77-4.90 (1H, m), 4.29 (1H, dd, J=7.08, 5.86 Hz), 3.95 (1H, t, J=5.33 Hz), 3.09 (1H, s), 2.91 (2H, t, J=7.39 Hz), 2.64-2.78 (1H, m), 2.44-2.63 (3H, m), 2.14-2.41 (2H, m), 1.75-1.98 (2H, m), 1.48-1.68 (3H, m), 1.35 (9H, s), 1.04 (6H, dd, J=12.33, 6.55 Hz).

Workup

  1. customThe reaction mixture was then evaporated in vacuo
  2. additionMeOH (2 ml) was added to the residue
  3. temperaturecooled to 0° C
  4. customevaporated to dryness
  5. filtrationThe product was filtered though a short silica gel column
  6. washeluting with 7N ammonia in MeOH
  7. customThis gave separation of two products
  8. additiona mixture of both
  9. custompurified on a prep
  10. washTLC plate, eluting twice with 7N ammonia in MeOH:DCM (1:9)

Sources & evidence

ORD record
ord-18a48ffb07594e7380e5f8436f952db7
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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