1-N-Boc-4-Piperidinecarboxylic acid methyl ester → 4-(6-Iodo-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester

HRID 657199Notes

Reaction equation

HRID 657199 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([I:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1.[CH3:28][O:29][C:30]([CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]1)=[O:31]>>[CH3:28][O:29][C:30]([C:32]1([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([I:12])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH2:37]1)=[O:31]

Participants

4

Reactant 3

HCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 111738094-Chloro-6-iodoquinazolineHCID 23714775LiHMDS tetrahydrofuran

Product 1

HCID 587708544-(6-Iodo-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester

Procedure

Prepared essentially as described in Example 1c using 4-chloro-6-iodo-quinazoline, as prepared in the preceding step, 1.1 eq LiHMDS/THF and 1.1 eq piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester, as prepared in Example 1b, and stirring at rt for 14 h following enolate formation at −78° C. The homogeneous brown solution was worked up as described in Example 1c to provide the impure crude title compound as a very dark brown thick oil (14.97 g). 1H-NMR (300 MHz, CDCl3) δ 9.28 (s, 1H), 8.41 (d, 1H), 8.10 (dd, 1H), 7.80 (d, 1H), 3.8-3.5 (m, 4H), 3.66 (s, 3H), 2.45-2.35 (m, 4H), 1.46 (s, 9H). LC/MS (ESI): calcd mass 497.1, found 398.0 (MH-Boc)+.

Workup

  1. customPrepared essentially
  2. customas prepared in Example 1b
  3. customat −78° C

Sources & evidence

ORD record
ord-f385798950164256a472a94e1bd2d981
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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