Methanol → HCID 178457040, compound

HRID 511633Notes

Reaction equation

HRID 511633 reaction equation
[C:1]([C:5]1[CH:52]=[CH:51][C:8]2[N:9](COCC[Si](C)(C)C)[C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([CH2:17][N:18]([CH2:22][C@@H:23]4[C@H:27]5[O:28]C(C)(C)[O:30][C@H:26]5[C@H:25]([N:33]5[C:37]6[N:38]=[CH:39][N:40]=[C:41]([NH2:42])[C:36]=6[CH:35]=[CH:34]5)[CH2:24]4)[CH:19]([CH3:21])[CH3:20])[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CO>Cl>[NH2:42][C:41]1[C:36]2[CH:35]=[CH:34][N:33]([C@@H:25]3[CH2:24][C@H:23]([CH2:22][N:18]([CH2:17][CH:15]4[CH2:14][CH:13]([CH2:12][C:10]5[NH:9][C:8]6[CH:51]=[CH:52][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][C:7]=6[N:11]=5)[CH2:16]4)[CH:19]([CH3:20])[CH3:21])[C@@H:27]([OH:28])[C@H:26]3[OH:30])[C:37]=2[N:38]=[CH:39][N:40]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 677748577-[(3aS,4R,6R,6aR)-6-{[({3-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutyl}methyl)(propan-2-yl)amino]methyl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 178457040HCID 178457040, compoundYield 55.2%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

7-[(3aS,4R,6R,6aR)-6-{[({3-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutyl}methyl)(propan-2-yl)amino]methyl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (58.7 mg, 0.08 mmol) was dissolved in conc. HCl solution (5 ml) and methanol (5 ml) and heated to 40° C. for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue partitioned between sat. NaHCO3(aq) (10 ml) and EtOAc (10 ml). The layers were separated and the aqueous layer was extracted with EtOAc (2×10 ml), the combined organics were then dried (MgSO4) and concentrated. The crude material was purified by prep TLC, eluting with 10% 2M NH3 in MeOH in DCM to afford the title compound (24.7 mg, 55%) as a colourless gum: MS (ESI+) for C32H45N7O2 m/z 560.4 [M+H]+; LC purity 100% (UV), (ret. time, 5.10 min); 1H NMR (500 MHz, Acetone) δH 8.12 (s, 1H), 7.30-7.60 (m, 2H), 7.13-7.28 (m, 2H), 6.54 (d, J=3.5 Hz, 1H), 6.33 (br. s., 1H), 4.85-5.07 (m, 1H), 4.36 (t, J=6.2 Hz, 1H), 4.08 (t, J=5.2 Hz, 1H), 3.01 (d, J=7.7 Hz, 1H), 2.93 (d, J=7.4 Hz, 2H), 2.78 (br. s., 2H), 2.59-2.73 (m, 2H), 2.15-2.56 (m, 7H), 1.68 (dt, J=12.4, 9.7 Hz, 1H), 1.44-1.62 (m, 2H), 1.35 (s, 9H), 0.90-1.07 (m, 6 II).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue partitioned between sat. NaHCO3(aq) (10 ml) and EtOAc (10 ml)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×10 ml)
  5. dry with materialthe combined organics were then dried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by prep TLC
  8. washeluting with 10% 2M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-2c703f71eb204e31a3e6fb5b844fd63e
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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